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Comprehensive Summary: Carbonic anhydrase accounts for catalytic reaction of CO2/HCO3– transformation, thus resulting in neutralization and acidification of the cellular environment, thereby favoring tumor development. Hence, it is a classical protein model of greatly biocatalytic significance as well as a highly expressed biomarker with renal tumor. We herein proposed a single‐molecule measurement on carbonic anhydrase using MspA nanopore, in [BMIM+] and asymmetric K+/Ca2+ cationic coordinated environment, instead of usual symmetric KCl/NaCl electrolyte. Significantly, our empirical analysis showed that asymmetric K+/Ca2+ cationic environment contributes to distinguishable current modulations, thus yielding better resolution for carbonic anhydrase measurement, which is independent of applied voltage and more importantly, is stable enough at varied pH conditions and for very low concentration test in urine sample. Our results provide a classical model for nanopore protein analysis, and may also permit biocatalytic measurement at single‐molecule level. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Carbonic anhydrase accounts for catalytic reaction of CO2/HCO3– transformation, thus resulting in neutralization and acidification of the cellular environment, thereby favoring tumor development. Hence, it is a classical protein model of greatly biocatalytic significance as well as a highly expressed biomarker with renal tumor. We herein proposed a single‐molecule measurement on carbonic anhydrase using MspA nanopore, in [BMIM+] and asymmetric K+/Ca2+ cationic coordinated environment, instead of usual symmetric KCl/NaCl electrolyte. Significantly, our empirical analysis showed that asymmetric K+/Ca2+ cationic environment contributes to distinguishable current modulations, thus yielding better resolution for carbonic anhydrase measurement, which is independent of applied voltage and more importantly, is stable enough at varied pH conditions and for very low concentration test in urine sample. Our results provide a classical model for nanopore protein analysis, and may also permit biocatalytic measurement at single‐molecule level. [ABSTRACT FROM AUTHOR]

Purpose: TRPC5 belongs to the mammalian superfamily of transient receptor potential (TRP) Ca2+-permeable cationic channels and it has been implicated in various CNS disorders. As part of our ongoing interest in the development of a PET radiotracer for imaging TRPC5, herein, we explored the radiosynthesis, and in vitro and in vivo evaluation of a new C-11 radiotracer [11C]HC070 in rodents and nonhuman primates. Procedures: [11C]HC070 was radiolabeled utilizing the corresponding precursor and [11C]CH3I via N-methylation protocol. Ex vivo biodistribution study of [11C]HC070 was performed in Sprague–Dawley rats. In vitro autoradiography study was conducted for the rat brain sections to characterize the radiotracer distribution in the brain regionals. MicroPET brain imaging studies of [11C]HC070 were done for 129S1/SvImJ wild-type mice and 129S1/SvImJ TRPC5 knockout mice for 0–60-min dynamic data acquisition after intravenous administration of the radiotracer. Dynamic PET scans (0–120 min) for the brain of cynomolgus male macaques were performed after the radiotracer injection. Results: [11C]HC070 was efficiently prepared with good radiochemical yield (45 ± 5%, n = 15), high chemical and radiochemical purity (> 99%), and high molar activity (320.6 ± 7.4 GBq/μmol, 8.6 ± 0.2 Ci/μmol) at the end of bombardment (EOB). Radiotracer [11C]HC070 has good solubility in the aqueous dose solution. The ex vivo biodistribution study showed that [11C]HC070 had a quick rat brain clearance. Autoradiography demonstrated that [11C]HC070 specifically binds to TRPC5-enriched regions in rat brain. MicroPET study showed the peak brain uptake (SUV value) was 0.63 in 129S1/SvImJ TRPC5 knockout mice compared to 1.13 in 129S1/SvImJ wild-type mice. PET study showed that [11C]HC070 has good brain uptake with maximum SUV of ~ 2.2 in the macaque brain, followed by rapid clearance. Conclusions: Our data showed that [11C]HC070 is a TRPC5-specific radiotracer with high brain uptake and good brain washout pharmacokinetics in both rodents and nonhuman primates. The radiotracer is worth further investigating of its suitability to be a PET radiotracer for imaging TRPC5 in animals and human subjects in vivo. [ABSTRACT FROM AUTHOR]

Spontaneous periodic up and down transitions of membrane potentials are considered to be a significant spontaneous activity of slow-wave sleep. Previous theoretical studies have shown that stimulation frequency and the dynamics of intrinsic currents have a major influence on synchronicity and firing rate of spontaneous fluctuation. Energy consumption is driven by internal spontaneous activity. However, its energy consumption and energy efficiency are not clear. Therefore, this article simulates the up and down transitions based on a neural network and discusses the energy consumption and energy efficiency. It is found that the dynamics of intrinsic currents have a great impact on the energy consumption and energy efficiency in the process. The energy consumption is influenced by the size of the period and the average power consumption of the state. The average power consumption by the up state is always greater than the consumption by the down state, and the energy consumption of the transition is more than firing. In addition, the lower average proportion of duration of the up state in the cycle leads to higher energy efficiency. Energy consumption is reduced and energy efficiency is enhanced by adjusting parameters of the network. The study helps us to understand and further explore the metabolic consumption of spontaneous activities. [ABSTRACT FROM AUTHOR]

[Display omitted] • 2,2′-bipyridine-based covalent triazine frameworks (bipCTF) is synthesized. • The bipCTF is introduced in SOPBI to form a bipCTF/SP-100 membrane. • The bipCTF creates a positively charged nanoscale ion channel in SOPBI. • The bipCTF/SP-100 membrane enhances proton conductivity and ion selectivity. • The fabricated membrane delivers good energy efficiency and capacity retention. The vanadium redox flow batteries (VRFBs) are an essential pathway to long-duration energy storage with the merits of power and energy decoupling, long lifetime and safety. However, low coulombic efficiency stemming from vanadium crossover across the membrane together with notable ohmic loss originated from low proton conductivity of the membrane still limits high performance operation of the VRFBs. Herein, we proposed 2,2′-bipyridine-based covalent triazine frameworks (bipCTF) crosslinked sulfonated-poly (4,4′-diphenylether-5,5′-bibenzimidazole) (SOPBI) (bipCTF/SP-100) for use as the membrane in VRFBs, which synergistically prevents vanadium crossover and enhances proton conductivity. By delicately tuning the sulfonation degree and properly incorporate bipCTF, the bipCTF/SP-100 membrane is successfully synthesized based on OPBI polymers, which delivers a reduced area resistance of 0.3 Ω cm2 and a low VO2+ permeability of 19.05 × 10−9 cm2 s−1, affording an excellent trade-off between proton conductivity and ion selectivity. Theoretical calculation further corroborates that the high proton conductivity of bipCTF/SP-100 is attributed to the ionic channels formed by bipCTF, while the superior ion selectivity is assigned to protonated imidazole and pyridine. Benefiting from microporous bipCTF/SP-100 membrane, the VRFB exhibits a high CE of 99.8 % and an excellent EE of 78.3 % at 250 mA cm−2 and meanwhile yields a high capacity retention of 94.8 % after 200 cycles at 200 mA cm−2, which shows enormous potential for high power density operation of the VRFBs. [ABSTRACT FROM AUTHOR]

It has been found that arsenic trioxide (ATO) is effective in treating acute promyelocytic leukemia (APL). However, long QT syndrome was reported in patients receiving therapy using ATO, which even led to sudden cardiac death. The underlying mechanisms of ATO-induced cardiotoxicity have been investigated in some biological experiments, showing that ATO affects human ether-à-go-go-related gene (hERG) channels, coding rapid delayed rectifier potassium current (IKr), as well as L-type calcium (ICaL) channels. Nevertheless, the mechanism by which these channel reconstitutions induced the arrhythmia in ventricular tissue remains unsolved. In this study, a mathematical model was developed to simulate the effect of ATO on ventricular electrical excitation at cellular and tissue levels by considering ATO’s effects on IKr and ICaL. The ATO-dose-dependent pore block model was incorporated into the IKr model, and the enhanced degree of ATO to ICaL was based on experimental data. Simulation results indicated that ATO extended the action potential duration of three types of ventricular myocytes (VMs), including endocardial cells (ENDO), midmyocardial cells (MCELL), and epicardial cells (EPI), and exacerbated the heterogeneity among them. ATO could also induce alternans in all three kinds of VMs. In a cable model of the intramural ventricular strand, the effects of ATO are reflected in a prolonged QT interval of simulated pseudo-ECG and a wide vulnerable window, thus increasing the possibility of spiral wave formation in ventricular tissue. In addition to showing that ATO prolonged QT, we revealed that the heterogeneity caused by ATO is also an essential hazard factor. Based on this, a pharmacological intervention of ATO toxicity by resveratrol was undertaken. This study provides a further understanding of ATO-induced cardiotoxicity, which may help to improve the treatment for APL patients.

Infrared neural stimulation (INS), as a novel form of neuromodulation, allows modulating the activity of nerve cells through thermally induced capacitive currents and thermal sensitivity ion channels. However, fundamental questions remain about the exact mechanism of INS and how the photothermal effect influences the neural response. Computational neural modeling can provide a powerful methodology for understanding the law of action of INS. We developed a temperature-dependent model of ion channels and membrane capacitance based on the photothermal effect to quantify the effect of INS on the direct response of individual neurons and neuronal networks. The neurons were connected through excitatory and inhibitory synapses and constituted a complex neuronal network model. Our results showed that a slight increase in temperature promoted the neuronal spikes and enhanced network activity, whereas the ultra-temperature inhibited neuronal activity. This biophysically based simulation illustrated the optical dose-dependent biphasic cell response with capacitive current as the core change condition. The computational model provided a new sight to elucidate mechanisms and inform parameter selection of INS. [ABSTRACT FROM AUTHOR]

In Alzheimer's disease, ion permeability through the ionic channel formed by Aβ peptides on cellular membranes appears to underlie neuronal cell death. An understanding of the formation mechanism of the toxic ionic channel by Aβ peptides is very important, but remains unclear. Our simulation results demonstrated the dynamics and mechanism of channel formation by Aβ1-28 peptides on the DPPC and POPC membrane by the coarse-grained method. The ionic channel formation is driven by the gyration of the radius and solvent accessible molecular surface area of Aβ1-28 peptides. The ionic channel formation mechanism was explored by the free energy profile based on the distribution of the gyration of the radius and solvent accessible molecular surface area of Aβ1-28 peptides on the fluid membrane. The stability and water permeability of the ionic channel formed by Aβ peptides was investigated by all-atomic model simulation. Our simulation showed that the ionic channel formed by Aβ1-28 peptides is very stable and has a good water permeability. This could help us to understand the pore formation mechanism by Aβ1-28 peptides on the fluidic membrane. It also provides us with a guideline by which to understand the toxicity of Aβ1-28 peptides' pores to the cell. [ABSTRACT FROM AUTHOR]

• A hydrogel electrolyte with lean-water matrix and hydrophilic interface is formed. • The hydrogel with ionic channels offers high ionic conductivity. • The hydrogel can suppress Zn dendrites and the side reactions on Zn anode. • The assembled cells delivers excellent cycle stability and high specific capacity. Although rechargeable aqueous zinc-ion batteries (ZIBs) are regarded as promising energy storage devices, the uncontrollable Zn dendrite and undesirable side reactions severely limit their practical applications. Herein, an anionic hydrogel electrolyte PAM/SA with 3D porous structures is developed by integrating sodium alginate (SA) and polyacrylamide (PAM) networks for highly reversible Zn plating/stripping. Mechanically enhanced and lean-water PAM/SA hydrogel with anionic chains for constructing ionic channels and molecular lubrication films, which facilitate Zn2+ migration for a high ionic conductivity (5.4 S m−1) and Zn2+ transference number (0.86) even under lean-water conditions (about 60%). Based on the experimental and theoretical analysis, the SA chain with strong coordination ability endows PAM/SA with improved desolvation kinetics and the ability to regulate the electric field intensity at the electrode/electrolyte interface, which is beneficial for suppressing side reactions and facilitating directional Zn deposition. Subsequently, the symmetric Zn//Zn cell based on PAM/SA hydrogel electrolyte delivers stable cycles for over 1800 h. The assembled Zn//V 2 O 5 battery based on PAM/SA reveals a high specific capacity and a long cycle life. This work provides a new insight for developing hydrogel electrolytes with high ionic conductivity and lean-water properties toward stable Zn anode [ABSTRACT FROM AUTHOR]

Locomotion is a fundamental movement in vertebrates produced by spinal networks known as central pattern generators (CPG). During fictive locomotion cat lumbar motoneurons (MNs) exhibit changes in membrane properties, including hyperpolarization of voltage threshold, reduction of afterhyperpolarization and input resistance, and amplification of nonlinear membrane properties. Both modeling and electrophysiological studies suggest that these changes can be produced by upregulating voltage-gated sodium channel (VGSC), persistent sodium (NaP), or L-type calcium channel (LTCC) or downregulating delayed-rectifier potassium (K(DR)) or calcium-dependent potassium channel (KCa) in spinal MNs. Further studies implicate that these channel modulations increase motor output and facilitate MN recruitment. However, it remains unknown how the channel modulation of CPG networks or MN pools affects the rhythmic generation of locomotion and force production of skeletal muscle during locomotion. In order to investigate this issue, we built a two-level CPG model composed of excitatory interneuron pools (Exc-INs), coupled reciprocally with inhibitory interneuron pools (Inh-INs), and projected to the flexor-extensor MN pools innervating skeletal muscles. Each pool consisted of 100 neurons with membrane properties based on cat spinal neurons. VGSC, K(DR), NaP, KCa, LTCC, and H-current channels were included in the model. Simulation results showed that (1) upregulating VGSC, NaP, or LTCC or downregulating KCa in MNs increased discharge rate and recruitment of MNs, thus facilitating locomotor pattern formation, increased amplitude of electroneurogram (ENG) bursting, and enhanced force generation of skeletal muscles. (2) The same channel modulation in Exc-INs increased the firing frequency of the Exc-INs, facilitated rhythmic generation, and increased flexor-extensor durations of step cycles. (3) Contrarily, downregulation of NaP or LTCC in MNs or Exc-INs or both CPG (Exc-INs and Inh-INs) and MNs disrupted locomotor pattern and reduced or even blocked the ENG bursting of MNs and force generation of skeletal muscles. (4) Pharmacological experiments showed that bath application of 25 μM nimodipine or 2 μM riluzole completely blocked fictive locomotion in isolated rat spinal cord, consistent with simulation results. We concluded that upregulation of VGSC, NaP, or LTCC or downregulation of KCa facilitated rhythmic generation and force production during walking, with NaP and LTCC playing an essential role. [ABSTRACT FROM AUTHOR]

Locomotion is a fundamental movement in vertebrates produced by spinal networks known as central pattern generators (CPG). During fictive locomotion cat lumbar motoneurons (MNs) exhibit changes in membrane properties, including hyperpolarization of voltage threshold, reduction of afterhyperpolarization and input resistance, and amplification of nonlinear membrane properties. Both modeling and electrophysiological studies suggest that these changes can be produced by upregulating voltage-gated sodium channel (VGSC), persistent sodium (NaP), or L-type calcium channel (LTCC) or downregulating delayed-rectifier potassium (K(DR)) or calcium-dependent potassium channel (KCa) in spinal MNs. Further studies implicate that these channel modulations increase motor output and facilitate MN recruitment. However, it remains unknown how the channel modulation of CPG networks or MN pools affects the rhythmic generation of locomotion and force production of skeletal muscle during locomotion. In order to investigate this issue, we built a two-level CPG model composed of excitatory interneuron pools (Exc-INs), coupled reciprocally with inhibitory interneuron pools (Inh-INs), and projected to the flexor-extensor MN pools innervating skeletal muscles. Each pool consisted of 100 neurons with membrane properties based on cat spinal neurons. VGSC, K(DR), NaP, KCa, LTCC, and H-current channels were included in the model. Simulation results showed that (1) upregulating VGSC, NaP, or LTCC or downregulating KCa in MNs increased discharge rate and recruitment of MNs, thus facilitating locomotor pattern formation, increased amplitude of electroneurogram (ENG) bursting, and enhanced force generation of skeletal muscles. (2) The same channel modulation in Exc-INs increased the firing frequency of the Exc-INs, facilitated rhythmic generation, and increased flexor-extensor durations of step cycles. (3) Contrarily, downregulation of NaP or LTCC in MNs or Exc-INs or both CPG (Exc-INs and Inh-INs) and MNs disrupted locomotor pattern and reduced or even blocked the ENG bursting of MNs and force generation of skeletal muscles. (4) Pharmacological experiments showed that bath application of 25 μM nimodipine or 2 μM riluzole completely blocked fictive locomotion in isolated rat spinal cord, consistent with simulation results. We concluded that upregulation of VGSC, NaP, or LTCC or downregulation of KCa facilitated rhythmic generation and force production during walking, with NaP and LTCC playing an essential role.

In Alzheimer’s disease, ion permeability through the ionic channel formed by Aβ peptides on cellular membranes appears to underlie neuronal cell death. An understanding of the formation mechanism of the toxic ionic channel by Aβ peptides is very important, but remains unclear. Our simulation results demonstrated the dynamics and mechanism of channel formation by Aβ1-28 peptides on the DPPC and POPC membrane by the coarse-grained method. The ionic channel formation is driven by the gyration of the radius and solvent accessible molecular surface area of Aβ1-28 peptides. The ionic channel formation mechanism was explored by the free energy profile based on the distribution of the gyration of the radius and solvent accessible molecular surface area of Aβ1-28 peptides on the fluid membrane. The stability and water permeability of the ionic channel formed by Aβ peptides was investigated by all-atomic model simulation. Our simulation showed that the ionic channel formed by Aβ1-28 peptides is very stable and has a good water permeability. This could help us to understand the pore formation mechanism by Aβ1-28 peptides on the fluidic membrane. It also provides us with a guideline by which to understand the toxicity of Aβ1-28 peptides’ pores to the cell.

Spirulina platensis is a “super-food” and has attracted researchers’ attention due to its anti-inflammatory, antioxidant, and analgesic properties. Herein, we investigated the antinociceptive effects of Spirulina in different rodent behavior models of inflammatory pain. Male Swiss mice were treated with Spirulina (3–300 mg/kg, p.o.), indomethacin (10 mg/kg, p.o.), or vehicle (0.9% NaCl 10 mL/kg). Behavioral tests were performed with administration of acetic acid (0.6%, i.p.), formalin 2.7% (formaldehyde 1%, i.pl.), menthol (1.2 µmol/paw, i.pl.), cinnamaldehyde (10 nmol/paw, i.pl.), capsaicin (1.6 µg/paw, i.pl.), glutamate (20 µmol/paw, i.pl.), or naloxone (1 mg/kg, i.p.). The animals were also exposed to the rotarod and open field test to determine possible effects of Spirulina on locomotion and motor coordination. The quantitative phytochemical assays exhibited that Spirulina contains significant concentrations of total phenols and flavonoid contents, as well as it showed a powerful antioxidant effect with the highest scavenging activity. Oral administration of Spirulina completely inhibited the abdominal contortions induced by acetic acid (ED50 = 20.51 mg/kg). Spirulina treatment showed significant inhibition of formalin-induced nociceptive behavior during the inflammatory phase, and the opioid-selective antagonist markedly blocked this effect. Furthermore, our data indicate that the mechanisms underlying Spirulina analgesia appear to be related to its ability to modulate TRMP8 and TRPA1, but not by TRPV1 or glutamatergic system. Spirulina represents an orally active and safe natural analgesic that exhibits great therapeutic potential for managing inflammatory pain disorders.

A kind of side-chain type anion exchange membranes (AEMs) with high ionic conductivity and good comprehensive stability was prepared via direct modification of commercial engineering plastic polyketone with diamines through Paal-Knorr reaction and quaternization reaction. It was found that the amount of diamine can effectively tune the microphase morphology and properties of the prepared quaternized functionalized-polyketone anion exchange membranes (QAFPK-AEMs). The tensile strength was increased from 18.6 MPa to 38.6 MPa, and the ion exchange capacity (IEC) was increased from 1.11 mmol/g to 2.71 mmol/g depending on the amount of added diamine. The QAFPK-1-6-AEM with the IEC of 1.43 mmol/g showed the highest hydroxide conductivity of 65 mS/cm at 25 °C and 96.8 mS/cm at 80 °C. The high ionic conductivity was achieved through the establishment of effective ionic channels, and it maintained 70% of the initial ionic conductivity after the 192 h treatment in 2 mol/L KOH (aq) at 80 °C. Moreover, a peak power density of 129 mW/cm2 was achieved when the assembled single cell with QAFPK-1-6-AEM was operated at 50 °C. Thus, the prepared QAFPK-AEMs showed great potential applications for the anion exchange membrane fuel cells (AEMFCs). [ABSTRACT FROM AUTHOR]

• Sodium pump is localised in ram sperm middle piece. • Inhibition of sodium pump results in discrete modification in ram sperm kinematic. • Cryopreservation influences the sodium pump expression in ram sperm membrane. The goals of this study were to investigate (a) the localisation of Na+, K+-ATPase in ram sperm; (b) cryopreservation like-changes on median fluorescence intensity (MFI) and the expression of Na+, K+-ATPase on the sperm surface (labeled sperm); and (c) the influence of Na+, K+-ATPase inhibition on sperm kinematics. Exp. 1: pooled semen samples (n = 7) from four rams were diluted and frozen. The following sperm features were evaluated in fresh-diluted and post-thawed samples: MFI and expression of Na+, K+-ATPase (Bodipy® FL-Ouabain), plasma and acrosomal membrane integrity (IP; FITC-PNA), sperm viability and plasma membrane stability (Yo-Pro and Merocyanine), as well as sperm kinematics (CASA). Exp. 2: pooled semen samples (n = 5) from four rams were diluted and incubated in medium treated with or without Na+, K+-ATPase inhibitor (ouabain, 10−4 M). Sperm kinematics (CASA) were determined prior to (0 h) and after incubation (3 h). In both fresh and thawed sperm, Na+, K+-ATPase was localised in the middle piece and cryopreservation did not influence the MFI in sperm with intact plasma membranes. However, cryopreservation reduced (P < 0.05) the overall percentage of sperm labeled with Bodipy® FL-Ouabain. Compared to the control, the inhibition of Na+, K+-ATPase reduced VAP at 0 h and both VAP and VSL at 3 h (P < 0.05). Thus, Na+, K+-ATPase is localised in the middle piece of fresh diluted and thawed sperm, and cryopreservation reduces the percentage of sperm expressing Na+, K+-ATPase in their surface, with no influence on the MFI of sperm with intact plasma membranes. Despite its localisation, Na+, K+-ATPase inhibition results in discrete kinematic modifications to ram sperm. [ABSTRACT FROM AUTHOR]

Abstract: A novel strategy for fabricating nanocomposite anion exchange membranes (AEM), which can construct self‐assembled ionic channels via in situ Menshutkin reaction, is proposed. The TEM image of a nanocomposite AEM based on chloromethylated polysulfone (CMPSF) and functionalized polyhedral oligomeric silsesquioxane (POSS) confirms the existence of core‐shell clusters. The ionic conductivity of these nanocomposite AEMs shows a notable increase when the content of functionalized POSS exceeds the percolation threshold. Furthermore, the optimized nanocomposite AEM has higher ionic conductivity than the control AEM with similar ion‐exchange capacity due to the well‐developed morphology. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of neonatal rat cardiomyocyte supernatants at different state on the gene expression of action potential-related ion channels in rat bone marrow mesenchymal stem cells( MSCs). Methods Rat bone marrow MSCs and neonatal rat cardiomyocytes were cultured in vitro. The cells were divided into the MSCs group,5-azacytidine( 5-Aza) induction group,normal induction group,hypoxia-induced group,and cardiomyocyte group. The MSCs group was normally cultured MSCs. The MSCs in the 5-Aza group were induced by myocardial inducer 5-Aza,the MSCs in the normal induction group was induced by normal cardiomyocyte supernatant,the MSCs in the hypoxia-induced group were induced by hypoxic cardiomyocyte supernatant,and the MSCs in the cardiomyocyte group were normal myocardial cells without induction. The mRNA expression of sodium( SCN2a),potassium( Kv2. 1,Kv1. 4,Kir1. 1,EAG1),and calcium( CCHL2α) channels in the cell membranes of each group was detected by RT-PCR. Results The ion channel genes associated with cardiac action potentials were expressed on the membrane of MSCs. Compared with the MSCs group,the mRNA expression of SCN2a,Kv2. 1,Kir1. 1,EAG1,and CCHL2α increased in the other groups( P< 0. 05 or P <0. 01),and the expression of Kv1. 4 mRNA in the hypoxia-induced group and cardiomyocyte group increased( P < 0. 05 or P < 0. 01). However,there was no significant difference in the expression of various ion channel genes between the 5-Aza induction group,the normal induction group,and the hypoxia-induced group. Conclusion The expression of ion channelrelated genes increases in MSCs after induction of normal and hypoxia cardiomyocyte supernatants,which shows that the myocardial microenvironment contributes to the myocardial electrophysiological changes of /MSCs. [ABSTRACT FROM AUTHOR]

Rechargeable zinc−air batteries are deemed as the most feasible alternative to replace lithium−ion batteries in various applications. Among battery components, separators play a crucial role in the commercial realization of rechargeable zinc−air batteries, especially from the viewpoint of preventing zincate (Zn(OH)42−) ion crossover from the zinc anode to the air cathode. In this study, a new hydroxide exchange membrane for zinc−air batteries was synthesized using poly (2,6-dimethyl-1,4-phenylene oxide) (PPO) as the base polymer. PPO was quaternized using three tertiary amines, including trimethylamine (TMA), 1-methylpyrolidine (MPY), and 1-methylimidazole (MIM), and casted into separator films. The successful synthesis process was confirmed by proton nuclear magnetic resonance and Fourier-transform infrared spectroscopy, while their thermal stability was examined using thermogravimetric analysis. Besides, their water/electrolyte absorption capacity and dimensional change, induced by the electrolyte uptake, were studied. Ionic conductivity of PPO−TMA, PPO−MPY, and PPO−MIM was determined using electrochemical impedance spectroscopy to be 0.17, 0.16, and 0.003 mS/cm, respectively. Zincate crossover evaluation tests revealed very low zincate diffusion coefficient of 1.13 × 10−8, and 0.28 × 10−8 cm2/min for PPO−TMA, and PPO−MPY, respectively. Moreover, galvanostatic discharge performance of the primary batteries assembled using PPO−TMA and PPO−MPY as initial battery tests showed a high specific discharge capacity and specific power of ~800 mAh/gZn and 1000 mWh/gZn, respectively. Low zincate crossover and high discharge capacity of these separator membranes makes them potential materials to be used in zinc−air batteries.

We present BFComp , an automated framework based on Sum-Of-Squares (SOS) optimization and δ -decidability over the reals, to compute Bisimulation Functions (BFs) that characterize Input-to-Output Stability (IOS) of dynamical systems. BFs are Lyapunov-like functions that decay along the trajectories of a given pair of systems, and can be used to establish the stability of the outputs with respect to bounded input deviations. In addition to establishing IOS, BFComp is designed to provide tight bounds on the squared output errors between systems whenever possible. For this purpose, two SOS optimization formulations are employed: SOSP 1, which enforces the decay requirements on a discretized grid over the input space, and SOSP 2, which covers the input space exhaustively. SOSP 2 is attempted first, and if the resulting error bounds are not satisfactory, SOSP 1 is used to compute a Candidate BF (CBF). The decay requirement for the BFs is then encoded as a δ -decidable formula and validated over a level set of the CBF using the dReal tool. If dReal produces a counterexample containing the states and inputs where the decay requirement is violated, this pair of vectors is used to refine the input-space grid and SOSP 1 is iterated. By computing BFs that appeal to a small-gain theorem, the BFComp framework can be used to show that a subsystem of a feedback-composed system can be replaced–with bounded error–by an approximately equivalent abstraction, thereby enabling approximate model-order reduction of dynamical systems. The BFs can then be used to obtain bounds on the error between the outputs of the original system and its reduced approximation. To this end, we illustrate the utility of BFComp on a canonical cardiac-cell model, showing that the four-variable Markovian model for the slowly activating Potassium current I K s can be safely replaced by a one-variable Hodgkin–Huxley-type approximation. In addition to a detailed performance evaluation of BFComp , our case study also presents workarounds for systems with non-polynomial vector fields, which are not amenable to standard SOS optimizers. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cu 3 PS 4 can achieve highly reversible multiple conversion reactions via a superior ionic diffusion channel. • Cu 3 PS 4 potassium ion anodes exhibit the highest capacity of 649.3 mA h g−1 at a current density of 0.05 Ag. • Cu 3 PS 4 anodes showed an ultra-stable 3000 cycle life and high-rate capability up to 8 A/g. • The potassium ion battery exhibits an energy density of 82.5 W h Kg−1 over 800 cycles. • The potassium ion hybrid capacitor exhibits an energy density of 80.3 W h Kg−1 over 5000 cycles. The emerging conversion-type chalcogenide anode materials for potassium ion storage may propose high theoretical specific capacity (>600 mA h g−1) and high compatibility with electrolytes, but currently the reported performance falls behind this goal due to severe material pulverization, polysulfide shuttle effect, and slow potassium ion diffusion during a charge/discharge process. Here, we report that Cu 3 PS 4 , a sulfur-rich orthorhombic metal phosphosulfide, can achieve highly reversible multiple conversion reactions, including the formation of KP and K 2 S along with 9 electrons transfer and efficient diffusion of potassium ions. Moreover, we introduce a layer graphite surface coating to enhance the overall conductivity of the electrodes, decrease the internal resistance, and render specific electronic channel with fast kinetic diffusion. During cycling, a tightly connected K-Cu P S junctions were formed to establish an ultra-stable heterostructure to entrap polysulfides in materials via an appropriate and uniform affinity. In electrochemical tests, Cu 3 PS 4 potassium ion anodes exhibit the highest capacity of 649.3 mA h g−1 at a current density of 0.05 A/g, reaching 94.4 % of its theoretical capacity (687.3 mA h g−1), and showed an ultra-stable 3000 cycle life and high-rate capability up to 8 A/g. Furthermore, the full battery and hybrid capacitor show attractive energy density and long cycle life of 82.5 W h kg−1 for 800 cycles and 80.3 W h kg−1 for 5000 cycles, respectively. This work provides promising results for metal phosphosulfide applications in high-efficiency potassium-ion storage devices, and may also be instructive for material advancements in related energy fields. [ABSTRACT FROM AUTHOR]

• The recent progress in dynamic supramolecular system in electrical conductive and magnetic [Ni(dmit)2] salts has been summarized. • Various molecular rotator and its application for dipole rotator has been exhibited. • Ferroelectrics coupled with dipole rotator in magnetic [Ni(dmit)2] salts has been summarized. • Design of dynamic structural units in magnetic [Ni(dmit)2] salts has been summarized. • The existing challenges and the future prospects of dynamic molecular system in the conductive and magnetic molecular materials are discussed. Supramolecular cation (SC) structures with high degrees of chemically designed freedoms are one of the most effective building blocks for controlling the dynamic and physical properties of molecular assemblies. Various SC structures, ranging from simple metal ions with different sizes, valences, and magnetic spins to organic ammoniums with diverse molecular structures, can be formed via complexation of crown ether derivatives with different ring sizes, which can be introduced into the π-planar Ni-coordination complexes using electrically conductive and magnetic [Ni(dmit) 2 ] salts (dmit2− = 2-thioxo-1,3-dithiole-4,5-dithiolate). Various dynamics such as ion transport, molecular rotation, and molecular oscillation coexist in a single crystal of [Ni(dmit) 2 ], affecting its electrical conductivity, magnetic behavior, dielectric response, and ferroelectricity. Unlike the physical properties exhibited by a static crystal lattice, the physical properties of a dynamic system depends on external factors such as temperature and the presence of an electric field. These properties are governed by factors such as the motional symmetry, amplitude, and frequency of the dynamic SC units in the crystal lattice. In particular, the dynamics of the polar structural units is particularly prominent in the dielectric response and ferroelectricity. The dipole rotator structure is an example of achieving macroscopic physical properties of ferroelectrics along with microscopic molecular dynamics. Structural and functional control of dynamic molecular assemblies using the SC approach is fundamental to the fabrication of next-generation molecular electronic and mechatronic devices. [ABSTRACT FROM AUTHOR]

Spontaneous periodic up and down transitions of membrane potentials are considered to be a significant spontaneous activity of slow-wave sleep. Previous theoretical studies have shown that stimulation frequency and the dynamics of intrinsic currents have a major influence on synchronicity and firing rate of spontaneous fluctuation. Energy consumption is driven by internal spontaneous activity. However, its energy consumption and energy efficiency are not clear. Therefore, this article simulates the up and down transitions based on a neural network and discusses the energy consumption and energy efficiency. It is found that the dynamics of intrinsic currents have a great impact on the energy consumption and energy efficiency in the process. The energy consumption is influenced by the size of the period and the average power consumption of the state. The average power consumption by the up state is always greater than the consumption by the down state, and the energy consumption of the transition is more than firing. In addition, the lower average proportion of duration of the up state in the cycle leads to higher energy efficiency. Energy consumption is reduced and energy efficiency is enhanced by adjusting parameters of the network. The study helps us to understand and further explore the metabolic consumption of spontaneous activities. NEW & NOTEWORTHY We use a more biological neural network to explore energy consumption and energy efficiency of up and down transitions. Specifically, we find that average energy consumption is more than that caused by action potentials, which proves that metabolic consumption is acquired substantially in the resting state as well. We also find that energy efficiency is influenced by the proportion of duration of the up state in the cycle. These findings may further improve the economy of the nervous system.

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Spontaneous periodic up and down transitions are considered to be a significant phenomenon that is characteristic of slow-wave sleep. We studied a neural network model of spontaneous up and down transitions based on our former study of a single-neuron model. We expanded the model by using two types of neurons-excitatory and inhibitory neurons-and redefining the connecting function between two neurons instead of assuming a constant connection, so that the model is closer to the in vivo network. Using this model, we studied the relationship between the transitions and network parameters such as size, structure and the ratio of excitatory to inhibitory neurons. We found that the network parameters have little impact on these spontaneous periodic up and down transitions. However, the intrinsic currents were found to play a leading role in the process. Then, we studied the transitions in the presence of stimulation and found that the addition of stimulation did have an effect on the network transitions. Through the observation and analysis of the findings, we have tried to explain the dynamics of up and down transitions and to lay the foundation for future work on the role of these transitions in cortex activity. [ABSTRACT FROM AUTHOR]

Bu makalede, iyonik kanal aktivasyon ve inaktivasyon kapılarının dinamik davranışı için yol ihtimaliyet yöntemine dayalı olarak elde edilen alternatif denklemler sunulmaktadır. Gerilim-kapılı iyonik kanalın dinamik davranışı, geleneksel Hodgkin-Huxley (H-H) matematiksel biçimciliği ile modellenmektedir. Bu modelde kanal iletkenliği, aktivasyon ve inaktivasyon kapılarına göre tanımlanmaktadır. Aktivasyon ve inaktivasyon kapılarının dinamiği, kapı değişkenine ve membran potansiyeline bağlı birinci dereceden diferansiyel denklemlerle modellenmektedir. Bu çalışmada sunulan yeni yaklaşımda, aktivasyon ve inaktivasyon kapısının dinamik davranışı, istatistik fizikte yaygın olarak kullanılan yol ihtimaliyet yöntemi kullanılarak iç enerji ve membran potansiyeline bağlı birinci dereceden diferansiyel denklemlerle modellenmektedir. Yeni model, H-H modelinde açıkça kullanılan zaman sabiti ve sürekli-hal değerlerini de gerektirmemektedir. Sayısal sonuçlar önerilen yöntemin geçerliliğini göstermektedir.

In order to simulate the guinea pig ventricular action potential we used the mathematical model developed by Luo and Rudy. This model contains 22 ionic channels represented by non linear differential equations. The mathematical models give us a tool to demonstrate through the simulation, how the (Basic Cycle Length) BCL changes the normal value of BCL changes the normal value of Vmax & and the Action Potential Action Potential duration (APD).

We show that in the context of the Iyer et al. (IMW) 67-variable cardiac myocycte model, it is possible to replace the detailed 13-state probabilistic subsystem of the sodium channel dynamics with a much simpler Hodgkin-Huxley (HH)-like two-state abstraction, while only incurring a bounded approximation error. We then extend our technique to the 10-state subsystem of the fast-recovering calcium-independent potassium channel. The basis of our results is the construction of an approximate bisimulation between the HH-type abstraction and the corresponding detailed ion channel model, both of which are input-controlled (voltage in this case) CTMCs. The construction of the appropriate approximate bisimulation, as well as the overall result regarding the behavior of this modified IMW model, involves: (1) Identification of the voltage-dependent parameters of the m and h gates in the HH-type models via a two-step fitting process, carried out over more than 20,000 representative observational traces of the detailed sodium and potassium ion channel models. (2) Proving that the distance between observations of the detailed models and their respective abstraction is bounded. (3) Exploring the sensitivity of the overall IMW model to the HH-type approximations. Our extensive simulation results experimentally validate our findings, for varying IMW-type input stimuli. [ABSTRACT FROM AUTHOR]

It has been found that arsenic trioxide (ATO) is effective in treating acute promyelocytic leukemia (APL). However, long QT syndrome was reported in patients receiving therapy using ATO, which even led to sudden cardiac death. The underlying mechanisms of ATO-induced cardiotoxicity have been investigated in some biological experiments, showing that ATO affects human ether-à-go-go-related gene (hERG) channels, coding rapid delayed rectifier potassium current ( I Kr ), as well as L-type calcium ( I CaL ) channels. Nevertheless, the mechanism by which these channel reconstitutions induced the arrhythmia in ventricular tissue remains unsolved. In this study, a mathematical model was developed to simulate the effect of ATO on ventricular electrical excitation at cellular and tissue levels by considering ATO's effects on I Kr and I CaL . The ATO-dose-dependent pore block model was incorporated into the I Kr model, and the enhanced degree of ATO to I CaL was based on experimental data. Simulation results indicated that ATO extended the action potential duration of three types of ventricular myocytes (VMs), including endocardial cells (ENDO), midmyocardial cells (MCELL), and epicardial cells (EPI), and exacerbated the heterogeneity among them. ATO could also induce alternans in all three kinds of VMs. In a cable model of the intramural ventricular strand, the effects of ATO are reflected in a prolonged QT interval of simulated pseudo-ECG and a wide vulnerable window, thus increasing the possibility of spiral wave formation in ventricular tissue. In addition to showing that ATO prolonged QT, we revealed that the heterogeneity caused by ATO is also an essential hazard factor. Based on this, a pharmacological intervention of ATO toxicity by resveratrol was undertaken. This study provides a further understanding of ATO-induced cardiotoxicity, which may help to improve the treatment for APL patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wan, Liu, Liu, Ma and Zhang.)

The hybrid biological/polymeric solid‐state nanopore membrane offers several opportunities to combine the advantage of biological channel (selectivity) and material (robustness). Based on this technology, the challenge is to obtain selective ionic exchange membranes, with no energy intake. The direct insertion of an ionic channel inside a nanopore should be a promise solution. Here, the authors report a hybrid nanopore based on nystatin A1 confinement in commercial nanopore membrane. Ionic transport and selectivity studies show that the hybrid nanopores exhibit mainly an anionic behaviour, on the contrary to biological conditions. However, the order of magnitude between the different ratios of permeation of several cationic species is retained even if the blocking of divalent cation is not totally proved. [ABSTRACT FROM AUTHOR]

Aims Fibroblasts, which play an important role in cardiac function/dysfunction, including arrhythmogenesis, have voltage-dependent (Kv) currents of unknown importance. Here, we assessed the differential expression of Kv currents between atrial and ventricular fibroblasts from control dogs and dogs with an atrial arrhythmogenic substrate caused by congestive heart failure (CHF). Methods and results Left atrial (LA) and ventricular (LV) fibroblasts were freshly isolated from control and CHF dogs (2-week ventricular tachypacing, 240 bpm). Kv currents were measured with whole-cell voltage-clamp, mRNA by quantitative polymerase chain reaction (qPCR) and fibroblast proliferation by 3H-thymidine incorporation. Robust voltage-dependent tetraethylammonium (TEA)-sensitive K+ currents (IC50 ∼1 mM) were recorded. The morphologies and TEA responses of LA and LV fibroblast Kv currents were similar. LV fibroblast Kv-current densities were significantly greater than LA, and Kv-current densities were significantly less in CHF than control. The mRNA expression of Kv-channel subunits Kv1.5 and Kv4.3 was less in LA vs. LV fibroblasts and was down-regulated in CHF, consistent with K+-current recordings. Ca2+-dependent K+-channel subunit (KCa1.1) mRNA and currents were less expressed in LV vs. LA fibroblasts. Inhibiting LA fibroblast K+ current with 1 mmol/L of TEA or KCa1.1 current with paxilline increased proliferation. Conclusions Fibroblast Kv-current expression is smaller in CHF vs. control, as well as LA vs. LV. KCa1.1 current is greater in LA vs. LV. Suppressing Kv current with TEA enhances fibroblast proliferation, suggesting that Kv current might act to check fibroblast proliferation and that reduced Kv current in CHF may contribute to fibrosis. Fibroblast Kv-current remodelling may play a role in the atrial fibrillation (AF) substrate; modulating fibroblast K+ channels may present a novel strategy to prevent fibrosis and AF. [ABSTRACT FROM PUBLISHER]

Soils in part of rice production areas have been seriously contaminated by cadmium (Cd). Rice with high Cd content over allowable limit produced in these areas is widely concerned. Low accumulation varieties can remarkably decrease the Cd content in rice as well as the risk of food safety. The translocation of Cd either from soil to root system or from roots to aboveground parts is identified by a lot of ion transport proteins. Transport efficiency of Cd in some rice varieties is regulated by special metal ionic transporters. However, most varieties transport Cd by cation transporters or universal ionic transporters. Both the expression levels and time of gens controlling ionic transporters directly influence the Cd transport rates inside rice plant and the accumulation amount in different organs. Screening and utilizing specific Cd transport genes are the genetic basis of breeding low accumulation varieties. [ABSTRACT FROM AUTHOR]

Abstract: Proton exchange membrane (PEM) with high proton conductivity is crucial to the commercial application of PEM fuel cell. Herein, sulfonated halloysite nanotubes (SHNTs) with tunable sulfonic acid group loading were synthesized and incorporated into sulfonated poly(ether ether ketone) (SPEEK) matrix to prepare nanocomposite membranes. Physicochemical characterization suggests that the well-dispersed SHNTs enhance the thermal and mechanical stabilities of nanocomposite membranes. The results of water uptake, ionic exchange capacity, and proton conductivity corroborate that the embedded SHNTs interconnect the ionic channels in SPEEK matrix and donate more continuous ionic networks. These networks then serve as proton pathways and allow efficient proton transfer with low resistance, affording enhanced proton conductivity. Particularly, incorporating 10% SHNTs affords the membrane a 61% increase in conductivity from 0.0152 to 0.0245 S cm−1. This study may provide new insights into the structure-properties relationships of nanotube-embedded conducting membranes for PEM fuel cell. [Copyright &y& Elsevier]

Background: Recent studies have demonstrated that atrial electrical remodeling was an important contributing factor for the occurrence, persistence and maintenance of atrial fibrillation. The expression changes of ionic channels, especially L-type calcium channel and potassium channel Kv4.3, were the important molecular mechanism of atrial electrical remodeling. This study aimed to observe the expression changes of ionic channels in a rapid paced cell model with primary cultured atrial myocytes. Methods: The primary rat atrial myocytes were cultured, characteristics of the cultured myocytes were observed with light microscope and the cell phenotype was harvested by immunocytochemical stain to detect α-actin. The cellular model of rapid pacing was established with primary cultured atrial myocytes. The expressions of L-type calcium channel α1c and potassium channel Kv4.3 in cultured atrial myocytes were detected by immunocytochemistry, reverse transcription polymerase chain reaction and Western blot after rapid pacing. Results: The primary rat atrial myocytes were isolated and cultured successfully, and used for following experiment by identification of activity and purity. Cellular model of rapid electrical field pacing was established successfully. There is no significant difference in cell activity after pacing compared to that before pacing by 3-[4, 5-dimethylthiazol-2-y1]-2, 5-diphenytetrazolium bromide assay, and cell degeneration can be observed by transmission electron microscope. The mRNA expression of L-type calcium channel α1c started to reduce after 6 h of rapid pacing and continued to decline as pacing continued. Protein expression changes were paralleled with decreased mRNA expression of the L-type calcium channel α1c. The mRNA expressions of potassium channel Kv4.3 were not altered within the first 6 h, but after 12 h, mRNA expressions were reduced. Longer pacing periods did not further decrease mRNA expression of potassium channel Kv4.3. Protein expression changes were paralleled with decreased mRNA expression of potassium channel Kv4.3. Conclusions: Rapid paced cultured atrial myocyte model was established utilized primary cultured atrial myocytes and this model can be used for studying the early electrical remodeling in atrial fibrillation. Expressions of L-type calcium channel α1c and potassium channel Kv4.3 were both reduced at different levels in early phase of rapid pacing atrial myocytes. It implicates the occurrence of ionic channel remodeling of atrial myocytes. [ABSTRACT FROM AUTHOR]

In this letter, we study the effect of cation charge on anion selectivity in the pore using grand canonical Monte Carlo simulations. The mechanism of anion selectivity inside nanopores was found to be primarily a consequence of the screening of negative charges by the cations. In the case of monovalent cations, screening was not very effective and anions were rejected. We found an 'off-state' at high pH and an 'on-state' at low pH. When there are divalent cations, screening is good and there is no rejection of the anion. The concentration of anions at high pH is similar to that at low pH. The system is always in an 'on-state'. Trivalent cations show an inverse selectivity mechanism: at high pH the concentration is higher than at low pH, i.e., the pore is in the 'on-state' at high pH and in the 'off-state' at low pH. [ABSTRACT FROM AUTHOR]

Infrared neural stimulation (INS), as a novel form of neuromodulation, allows modulating the activity of nerve cells through thermally induced capacitive currents and thermal sensitivity ion channels. However, fundamental questions remain about the exact mechanism of INS and how the photothermal effect influences the neural response. Computational neural modeling can provide a powerful methodology for understanding the law of action of INS. We developed a temperature-dependent model of ion channels and membrane capacitance based on the photothermal effect to quantify the effect of INS on the direct response of individual neurons and neuronal networks. The neurons were connected through excitatory and inhibitory synapses and constituted a complex neuronal network model. Our results showed that a slight increase in temperature promoted the neuronal spikes and enhanced network activity, whereas the ultra-temperature inhibited neuronal activity. This biophysically based simulation illustrated the optical dose-dependent biphasic cell response with capacitive current as the core change condition. The computational model provided a new sight to elucidate mechanisms and inform parameter selection of INS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wei, Li, Song, Du, Yang, Zhang and Liu.)

Taurine-magnesium coordination compound (TMCC) has anti-arrhythmic effects. The aim of the present study was to explore the targets of the anti-arrhythmic effect of TMCC and the electrophysiological effects of TMCC on ouabain-induced arrhythmias in rat ventricular myocytes. Sodium current ( I), L-type calcium current ( I), and transient outward potassium current ( I) were measured and analyzed using whole-cell patch-clamp recording technique in normal rat cardiac myocytes and rat ventricular myocytes of arrhythmia induced by ouabain. In isolated ventricular myocytes, I and I were blocked by TMCC (100, 200, 400 μM) in a concentration-dependent manner, and the effects of TMCC (400 μM) were equal to that of amiodarone. However, I was moderately increased by TMCC (400 μM) while significantly decreased by amiodarone. Ouabain (5 μM) significantly decreased sodium, L-type calcium, and transient outward potassium currents. TMCC (100 μM) relieved abnormal sodium currents induced by ouabain through facilitation of steady-state inactivation. TMCC (200 and 400 μM) relieved abnormal L-type calcium currents induced by ouabain through facilitation of steady-state activation and retardation of steady-state inactivation. TMCC failed to further inhibit abnormal transient outward potassium currents induced by ouabain. However, amiodarone inhibited the decreasing sodium, L-type calcium, and transient outward potassium currents further. These data suggest that I, I, and I may be the targets of the antiarrhythmic effect of TMCC, which can antagonize ouabain-induced changes of ionic currents in rat ventricular myocytes. [ABSTRACT FROM AUTHOR]

Abstract: We synthesized novel sulfonated star-hyperbranched polyimides composed of a hydrophobic hyperbranched polymer for polymer stability and a hydrophilic sulfonated polyimide as the proton-transport site in the core–shell structure. The proton conductivities of the star-hyperbranched polyimide membranes were measured as functions of the relative humidity and temperature using electrochemical impedance spectroscopy. Although the water uptake and IEC value for the sulfonated star-hyperbranched polyimide membranes were almost constant, the proton conductivity of the membrane strongly depended on the molecular weight of the hydrophilic sulfonated polyimide as the shell. Especially, the conductivity of the high molecular weight star-hyperbranched polyimide membranes was significantly superior to that determined in Nafion® at all temperatures and was 0.51Scm−1 at 80°C and 98% RH, which may suggest that a good proton-transport pathway in the core–shell structure is formed. Consequently, this material proved to be promising as a proton exchange membrane and may have potential applications for use in fuel cells. [Copyright &y& Elsevier]

Abstract: This article aims at making readers, experimentalists and theorists, more aware of the abstractions made by an observer when measuring and reporting behavioral and neural timescales. These abstractions stow away the fact that, above lower boundaries that reflect fairly well understood physical constraints, observed and reported timescales are often not intrinsic to the biological system; rather, in most cases they reflect conditions that are imposed by the observer through the measuring procedure. This is true at practically every level of organization, from behavior down to molecules. I analyze the impacts of the resulting temporal manifold in behavioral and brain sciences on experimental designs and mathematical modeling. [Copyright &y& Elsevier]

Ionic channels form pores in biomembranes. These pores are large macromolecular structures. Due to thermal fluctuations of countless degrees-of-freedom of the biomembrane material, the actual form of the pores is permanently subject to modification. Furthermore, the arrival of an ion at the binding site can change this form by repolarizing the surrounding aminoacids. In any case the variations of the pore structure are stochastic. In this paper, we discuss the effect of such modifications on the channel conductivity. Applying a simple kinetic description, we show that stochastic variations in channel properties can significantly alter the ionic current, even leading to its substantial increase or decrease for the specific matching of some time-scales of the system. [ABSTRACT FROM AUTHOR]

We have developed a model of the tetrameric ryanodine receptor—the calcium channel of the sarcoplasmic reticulum. The model accurately describes published experimental data on channel activity at various concentrations of Ca2+, caffeine and quercetin. The proposed mechanisms involve allosteric regulation of Ca2+ affinity by both caffeine and quercetin, and the existence of two independent, A- and I-gates controlled by Ca2+ binding to an activating and an inhibitory module of the receptor. There are four different configurations of the receptor that affect ligand binding to the activation module, but not to the inhibition module. Consequently, there are four kinetic modes for the A-gate and one mode for the I-gate. At a certain moment, the receptor can be in any of the four possible conformations with equal probability. By fitting the data we are able to derive ligand affinities and Hill coefficients, to describe the observation that quercetin is an activating agent stronger than caffeine, and that caffeine and quercetin activate the channel at very low Ca2+ concentration (∼10−11 M). We predict that the activation regime at saturating caffeine or quercetin should present four distinct regions at increasing Ca2+, corresponding to the four different gating modes. Another interesting prediction is the enlargement of the activity domain toward higher Ca2+ concentrations in the presence of caffeine or quercetin. [ABSTRACT FROM AUTHOR]

Abstract: The ability of three primary amphipathic Cell-Penetrating Peptides (CPPs) CH3-CO-GALFLGFLGAAGSTMGAWSQPKKKRKV-NH-CH2-CH2-SH, CH3-CO-GALFLAFLAAALS LMGLWSQPKKKRKV-NH-CH2-CH2-SH, and CH3-CO-KETWWETWWTEWSQPKKKRKV-NH-CH2-CH2-SH called Pβ, Pα and Pep-1, respectively, to promote pore formation is examined both in Xenopus oocytes and artificial planar lipid bilayers. A good correlation between pore formation and their structural properties, especially their conformational versatility, was established. This work shows that the cell-penetrating peptides Pβ and Pep-1 are able to induce formation of transmembrane pores in artificial bilayers and that these pores are most likely at the basis of their ability to facilitate intracellular delivery of therapeutics. In addition, their behaviour provides some information concerning the positioning of the peptides with respect to the membrane and confirms the role of the membrane potential in the translocation process. [Copyright &y& Elsevier]

Abstract: Neuregulin-1 (NRG-1) is an active component found in sciatic nerve conditioned medium (CM). NRG-1 is a growth and differentiation factor shown to have an effect on neuritogenesis and survival of neural cells. PC12 cells chronically treated with NRG-1 (β1 isoform) show an increase in proliferation under low-serum condition (2.5% fetal bovine serum and 1.25% horse serum) and serum deprivation, without visible morphological changes. NRG-1 and CM treatments of PC12 cells induced an increase of voltage-activated Ca2+ currents and large-conductance calcium-activated K+ currents (KCa). AG825, a specific inhibitor for erbB2 receptor, abolishes KCa current, though Ca2+ currents were not inhibited. These results showed that NRG-1 is capable of inducing functional changes but is not sufficient on its own to have an effect on cell morphology. [Copyright &y& Elsevier]

Interweaving strategies of electrophysiology, calcium imaging and immunocytochemistry bring new insights into the mode of action of the Brazilian scorpion Tityus serrulatusβ-toxin VII. Pacemaker dorsal unpaired median neurons isolated from the cockroach central nervous system were used to study the effects of toxin VII. In current-clamp, 50 nm toxin VII produced a membrane depolarization and reduced spiking. At 200 nm, depolarization associated with multiphasic effects was seen. After artificial hyperpolarization, plateau potentials on which spontaneous electrical activity appeared were observed. In voltage clamp, toxin VII induced a negative shift of the voltage dependence of sodium current activation without significant effect on steady-state inactivation. In addition, toxin VII produced a permanent TTX-sensitive holding inward current, indicating that background sodium channels were targeted by β-toxin. Cell-attached patch recordings indicated that these channels were switched from unclustered single openings to current fluctuating between distinct subconductance levels exhibiting increased open probability and open-time distribution. Toxin VII also produced a TTX-sensitive [Ca2+]i rise. Immunostaining with Cav2.2(α1b) antibodies and calcium imaging data obtained with ω-CgTx GVIA indicated that N-type high-voltage-activated calcium channels initiated calcium influx and were an essential intermediate in the pathway linking toxin VII-modified sodium channels to the activation of an additional route for calcium entry. By using inhibitors of (i) noncapacitative calcium entry (inhibitor LOE-908), (ii) NO-sensitive guanylyl cyclase (ODQ) and (iii) phosphodiesterase 2 (EHNA), together with cGMP antibodies, we demonstrated that noncapacitative calcium entry was the final step in a complex combination of events that was initiated by toxin VII-alteration of sodium channels and then involved successive activation of other membrane ion channels. [ABSTRACT FROM AUTHOR]

We have synthesized a novel sulfonated block copolyimide with long block chains by chemical imidization using a two-pot procedure. The proton conductivity of a block copolyimide film, i.e., NTDA-BDSA-b-6FAP(140/60) was approximately 0.45 S cm-1, which is higher than that of Nafioni117®. Additionally, we demonstrated that the proton conductivity of the block copolyimide film strongly depends on the block chain lengths. The conductivities of the block copolyimide films increased with increasing block chain lengths. This may be due to the formation of ionic channels in the copolyimide films and its dependence on the block chain length. We are currently investigating the effects of the morphology and domain size of the block copolyimide film on the proton conductivity. [ABSTRACT FROM AUTHOR]

Abstract: The cytotoxic activity of some of the most pathogenic strains of Vibrio cholerae is associated with a cytolysin protein (VCC), which forms oligomeric transmembrane pores and changes the permeability of intestinal cells. We present here a model structure of the transmembrane pore of VCC based on sequence comparison with other pore-forming toxins. VCC is suggested to form a transmembrane β-barrel pore with a relatively large trans vestibule region. Calculations of the electrostatic profile within the pore lumen provide a rationale for the low conductance and selectivity of the VCC ion channel. [Copyright &y& Elsevier]

This review is centered in the description of the molecular mechanisms of lead toxicity and its repercussion in the cellular excitability and central nervous system function. [ABSTRACT FROM AUTHOR]

A 3D stationary Langevin-Lorentz-Poisson (LLP) coupled model is presented to investigate the ion transport across excitable cell membranes in the presence of external ELF magnetic field. The strategy proposed is based on an iterative scheme which alternates the solution of a Poisson problem with the time-domain integration of the Langevin-Lorentz equation. A Fokker-Planck analysis of the latter equation is perfomed to compute the statistical parameters of ion motion. This approach has been especially set up in order to take into account explicitly the ion-ion interaction inside ionic channels which has not been considered in literature. The simulations performed show that ELF magnetic field of low intensity (100 μT) can effect significantly the dynamical parameters of ion motion inside the channel provided that the ion-ion interaction is considered. [ABSTRACT FROM AUTHOR]

This work reports the finding of a unique fast inward sodium current (INa) in MDA-MB-231 cells which is missing in MDA-MB-468 cells and in MCF-7 cells. This current is high-voltage-activated and displays a window current at the membrane potential of MDA-MB-231 cells. This current is blocked by high concentrations of tetrodotoxin (TTX). In MDA-MB-231 cells, which are the most invasive cells among the three cell lines tested, proliferation and migration were not sensitive to TTX while invasion was reduced by approximately 30%. These experiments suggest that INa is involved in the invasion process, probably through its participation to the regulation of the intracellular sodium homeostasis. [Copyright &y& Elsevier]

Sodium currents in cell lines transfected with the sole α-subunit, or constitutively expressing sodium channels, have an inactivation that is always prevalently mono-exponential. Differently, expression of α-subunit in Xenopus oocytes exerts slow inactivating currents with biphasic decay, while simultaneous co-transfection of α and β1 restores a mono-exponential (normal) inactivation. A hypothesis for such differences is that an endogenous presence of β1 or β1-alternative splicing, β1A, in cells could account for the normal inactivation. To test this hypothesis and to evaluate the role for the β1A, we inhibited the expression of β1/β1A by antisense oligonucleotides on Nav1.4-transfected human embryonic cell line 293 (HEK) cells. Reduction of β1/β1A produces no significant functional effects in Nav1.4-HEK. This result invalidates the hypothesis that the lack of slow-mode in cell lines is simply due to a constitutive expression of β1/β1A. [Copyright &y& Elsevier]

The aim of the present study was to evaluate the effects of quercetin-filled phosphatidylcholine liposomes (PCLs) on peroxynitrite (ONOO−)-induced cardiac arrhythmias. Experiments were done using different experimental models, including isolated rat papillary muscle, Langendorff perfused rat hearts, and anesthetized animals. Being exogenously applied in a concentration greater than 50 μ M, ONOO−, caused inhibition of isometric twitch amplitude in isolated papillary muscles and led to an appearance of arrhythmias. Decomposed ONOO− had no similar effects and reversibly increased twitch amplitude. Authentic nitric oxide (NO, 100 μ M) did not produce arrhythmias and had no significant effect on twitch amplitude. Verapamil and ruthenium red were with-out effect on ONOO−-induced arrhythmias, whereas tetrodotoxin and nicorandil effectively prevented arrhythmias development. Ouabain increased the arrhythmogenic effect of ONOO−. ONOO− significantly decreased coronary perfusion pressure (CPP) and mean left-ventricular pressure (MLVP) in the Langendorff perfused rat heart and produced severe arrhythmias. Authentic nitric oxide (NO) decreased CPP and MLVP insignificantly and resulted in a low incidence of arrhythmias. The NO donor SIN-1 in doses greater than 50 μ M led to the appearance of low-incidence arrhythmias in anesthetized rats. Intraventricular injection of ONOO− promotes the appearance of a high incidence of arrhythmias in anesthetized rats and decreased MLVP. PCLs filled with the antioxidant quercetin restored normal cardiac contractility in both isolated tissues and anesthetizes animals. In conclusion, we hypothesized that ONOO−, but not its decomposed products, can initiate membrane lipid peroxidation and damage the phospholipid environment of ionic channels in myocardial cell plasma membranes inducing abnormal cardiac action potentials, arrhythmogenesis, and contractile dysfunction. Quercetin-filled PCL provide reliable protection against peroxynitrite-induced myocardial injury in isolated cardiac tissues and anesthetized animals primarily as a result of the decomposition of endogenously formed ONOO−. [ABSTRACT FROM AUTHOR]