29 results on '"Zhou, Zhuan"'
Search Results
2. Ca 2+ -independent but voltage-dependent quantal catecholamine secretion (CiVDS) in the mammalian sympathetic nervous system.
- Author
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Huang R, Wang Y, Li J, Jiang X, Li Y, Liu B, Wu X, Du X, Hang Y, Jin M, Zhu F, Wang C, Chai Z, and Zhou Z
- Subjects
- Action Potentials, Animals, Mammals, Models, Biological, Muscle Cells metabolism, Neurons metabolism, Spinal Cord Dorsal Horn cytology, Spinal Cord Dorsal Horn metabolism, Synaptic Transmission, Calcium metabolism, Catecholamines metabolism, Chromaffin Cells metabolism, Sympathetic Nervous System metabolism
- Abstract
Action potential-induced vesicular exocytosis is considered exclusively Ca
2+ dependent in Katz's Ca2+ hypothesis on synaptic transmission. This long-standing concept gets an exception following the discovery of Ca2+ -independent but voltage-dependent secretion (CiVDS) and its molecular mechanisms in dorsal root ganglion sensory neurons. However, whether CiVDS presents only in sensory cells remains elusive. Here, by combining multiple independent recordings, we report that [1] CiVDS robustly presents in the sympathetic nervous system, including sympathetic superior cervical ganglion neurons and slice adrenal chromaffin cells, [2] uses voltage sensors of Ca2+ channels (N-type and novel L-type), and [3] contributes to catecholamine release in both homeostatic and fight-or-flight like states; [4] CiVDS-mediated catecholamine release is faster than that of Ca2+ -dependent secretion at the quantal level and [5] increases Ca2+ currents and contractility of cardiac myocytes. Together, CiVDS presents in the sympathetic nervous system with potential physiological functions, including cardiac muscle contractility., Competing Interests: The authors declare no conflict of interest.- Published
- 2019
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3. Ca V 2.2 Gates Calcium-Independent but Voltage-Dependent Secretion in Mammalian Sensory Neurons.
- Author
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Chai Z, Wang C, Huang R, Wang Y, Zhang X, Wu Q, Wang Y, Wu X, Zheng L, Zhang C, Guo W, Xiong W, Ding J, Zhu F, and Zhou Z
- Subjects
- Action Potentials drug effects, Animals, Caffeine pharmacology, Calcium Channel Blockers pharmacology, Cells, Cultured, Endoplasmic Reticulum drug effects, Endoplasmic Reticulum ultrastructure, Exocytosis drug effects, Exocytosis genetics, Ganglia, Spinal cytology, Ganglia, Spinal ultrastructure, Humans, Ion Channel Gating drug effects, Male, Membrane Fusion drug effects, Membrane Fusion genetics, Models, Molecular, Phosphodiesterase Inhibitors pharmacology, Presynaptic Terminals drug effects, Presynaptic Terminals physiology, Rats, Rats, Sprague-Dawley, Rats, Wistar, SNARE Proteins genetics, SNARE Proteins metabolism, Sensory Receptor Cells ultrastructure, Synaptic Transmission drug effects, Synaptic Transmission genetics, Transduction, Genetic, omega-Conotoxin GVIA pharmacology, Calcium metabolism, Calcium Channels, N-Type genetics, Calcium Channels, N-Type metabolism, Ion Channel Gating genetics, Sensory Receptor Cells physiology
- Abstract
Action potential induces membrane depolarization and triggers intracellular free Ca
2+ concentration (Ca2+ )-dependent secretion (CDS) via Ca2+ influx through voltage-gated Ca2+ channels. We report a new type of somatic exocytosis triggered by the action potential per se-Ca2+ -independent but voltage-dependent secretion (CiVDS)-in dorsal root ganglion neurons. Here we uncovered the molecular mechanism of CiVDS, comprising a voltage sensor, fusion machinery, and their linker. Specifically, the voltage-gated N-type Ca2+ channel (CaV 2.2) is the voltage sensor triggering CiVDS, the SNARE complex functions as the vesicle fusion machinery, the "synprint" of CaV 2.2 serves as a linker between the voltage sensor and the fusion machinery, and ATP is a cargo of CiVDS vesicles. Thus, CiVDS releases ATP from the soma while CDS releases glutamate from presynaptic terminals, establishing the CaV 2.2-SNARE "voltage-gating fusion pore" as a novel pathway co-existing with the canonical "Ca2+ -gating fusion pore" pathway for neurotransmitter release following action potentials in primary sensory neurons., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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4. Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium.
- Author
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Fan H, Du X, Zhang J, Zheng H, Lu X, Wu Q, Li H, Wang H, Shi Y, Gao G, Zhou Z, Tan DX, and Li X
- Subjects
- Cholesterol metabolism, Ebolavirus metabolism, Hemorrhagic Fever, Ebola prevention & control, Hep G2 Cells, Humans, Receptors, Estrogen metabolism, Sphingosine metabolism, Up-Regulation, Calcium metabolism, Ebolavirus drug effects, Endosomes metabolism, Hemorrhagic Fever, Ebola metabolism, Lysosomes metabolism, Selective Estrogen Receptor Modulators pharmacology
- Abstract
The Ebola crisis occurred in West-Africa highlights the urgency for its clinical treatments. Currently, no Food and Drug Administration (FDA)-approved therapeutics are available. Several FDA-approved drugs, including selective estrogen receptor modulators (SERMs), possess selective anti-Ebola activities. However, the inhibitory mechanisms of these drugs remain elusive. By analyzing the structures of SERMs and their incidental biological activity (cholesterol accumulation), we hypothesized that this incidental biological activity induced by SERMs could be a plausible mechanism as to their inhibitory effects on Ebola infection. Herein, we demonstrated that the same dosages of SERMs which induced cholesterol accumulation also inhibited Ebola infection. SERMs reduced the cellular sphingosine and subsequently caused endolysosomal calcium accumulation, which in turn led to blocking the Ebola entry. Our study clarified the specific anti-Ebola mechanism of SERMs, even the cationic amphiphilic drugs (CADs), this mechanism led to the endolysosomal calcium as a critical target for development of anti-Ebola drugs.
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- 2017
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5. Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons.
- Author
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Shang S, Zhu F, Liu B, Chai Z, Wu Q, Hu M, Wang Y, Huang R, Zhang X, Wu X, Sun L, Wang Y, Wang L, Xu H, Teng S, Liu B, Zheng L, Zhang C, Zhang F, Feng X, Zhu D, Wang C, Liu T, Zhu MX, and Zhou Z
- Subjects
- Acrolein, Animals, Calcitonin Gene-Related Peptide metabolism, Calcium Signaling, Endoplasmic Reticulum metabolism, Endosomes metabolism, Exocytosis, Hyperalgesia metabolism, Ion Channel Gating, Isothiocyanates, Male, Mice, Inbred C57BL, Neuropeptides metabolism, Solutions, TRPA1 Cation Channel, Calcium metabolism, Ganglia, Spinal metabolism, Intracellular Space metabolism, Lysosomes metabolism, Neurons metabolism, Transient Receptor Potential Channels metabolism
- Abstract
Transient receptor potential A1 (TRPA1) is a nonselective cation channel implicated in thermosensation and inflammatory pain. In this study, we show that TRPA1 (activated by allyl isothiocyanate, acrolein, and 4-hydroxynonenal) elevates the intracellular Ca
2+ concentration ([Ca2+ ]i ) in dorsal root ganglion (DRG) neurons in the presence and absence of extracellular Ca2+ Pharmacological and immunocytochemical analyses revealed the presence of TRPA1 channels both on the plasma membrane and in endolysosomes. Confocal line-scan imaging demonstrated Ca2+ signals elicited from individual endolysosomes ("lysosome Ca2+ sparks") by TRPA1 activation. In physiological solutions, the TRPA1-mediated endolysosomal Ca2+ release contributed to ∼40% of the overall [Ca2+ ]i rise and directly triggered vesicle exocytosis and calcitonin gene-related peptide release, which greatly enhanced the excitability of DRG neurons. Thus, in addition to working via Ca2+ influx, TRPA1 channels trigger vesicle release in sensory neurons by releasing Ca2+ from lysosome-like organelles., (© 2016 Shang et al.)- Published
- 2016
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6. Calcium influx activates adenylyl cyclase 8 for sustained insulin secretion in rat pancreatic beta cells.
- Author
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Dou H, Wang C, Wu X, Yao L, Zhang X, Teng S, Xu H, Liu B, Wu Q, Zhang Q, Hu M, Wang Y, Wang L, Wu Y, Shang S, Kang X, Zheng L, Zhang J, Raoux M, Lang J, Li Q, Su J, Yu X, Chen L, and Zhou Z
- Subjects
- Animals, Cells, Cultured, Cyclic AMP metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, Disease Models, Animal, Patch-Clamp Techniques, Rats, Rats, Wistar, Signal Transduction, Adenylyl Cyclases metabolism, Calcium metabolism, Insulin-Secreting Cells metabolism
- Abstract
Aims/hypothesis: Insulin is a key metabolic regulator in health and diabetes. In pancreatic beta cells, insulin release is regulated by the major second messengers Ca(2+) and cAMP: exocytosis is triggered by Ca(2+) and mediated by the cAMP/protein kinase A (PKA) signalling pathway. However, the causal link between these two processes in primary beta cells remains undefined., Methods: Time-resolved confocal imaging of fluorescence resonance energy transfer signals was performed to visualise PKA activity, and combined membrane capacitance recordings were used to monitor insulin secretion from patch-clamped rat beta cells., Results: Membrane depolarisation-induced Ca(2+) influx caused an increase in cytosolic PKA activity via activating a Ca(2+)-sensitive adenylyl cyclase 8 (ADCY8) subpool. Glucose stimulation triggered coupled Ca(2+) oscillations and PKA activation. ADCY8 knockdown significantly reduced the level of depolarisation-evoked PKA activation and impaired replenishment of the readily releasable vesicle pool. Pharmacological inhibition of PKA by two inhibitors reduced depolarisation-induced PKA activation to a similar extent and reduced the capacity for sustained vesicle exocytosis and insulin release., Conclusions/interpretation: Our findings suggest that depolarisation-induced Ca(2+) influx plays dual roles in regulating exocytosis in rat pancreatic beta cells by triggering vesicle fusion and replenishing the vesicle pool to support sustained insulin release. Therefore, Ca(2+) influx may be important for glucose-stimulated insulin secretion.
- Published
- 2015
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7. Extracellular Ca²⁺ per se inhibits quantal size of catecholamine release in adrenal slice chromaffin cells.
- Author
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Shang S, Wang C, Liu B, Wu Q, Zhang Q, Liu W, Zheng L, Xu H, Kang X, Zhang X, Wang Y, Zheng H, Wang S, Xiong W, Liu T, and Zhou Z
- Subjects
- Adrenal Glands cytology, Animals, Cells, Cultured, Chromaffin Cells cytology, Rats, Rats, Wistar, Adrenal Glands metabolism, Calcium metabolism, Catecholamines metabolism, Chromaffin Cells metabolism, Exocytosis physiology, Secretory Vesicles metabolism
- Abstract
Classic calcium hypothesis states that depolarization-induced increase in intracellular Ca(2+) concentration ([Ca(2+)]i) triggers vesicle exocytosis by increasing vesicle release probability in neurons and neuroendocrine cells. The extracellular Ca(2+), in this calcium hypothesis, serves as a reservoir of Ca(2+) source. Recently we find that extracellular Ca(2+)per se inhibits the [Ca(2+)]i dependent vesicle exocytosis, but it remains unclear whether quantal size is regulated by extracellular, or intracellular Ca(2+) or both. In this work we showed that, in physiological condition, extracellular Ca(2+) per se specifically inhibited the quantal size of single vesicle release in rat adrenal slice chromaffin cells. The extracellular Ca(2+) in physiological concentration (2.5 mM) directly regulated fusion pore kinetics of spontaneous quantal release of catecholamine. In addition, removal of extracellular Ca(2+) directly triggered vesicle exocytosis without eliciting intracellular Ca(2+). We propose that intracellular Ca(2+) and extracellular Ca(2+)per se cooperately regulate single vesicle exocytosis. The vesicle release probability was jointly modulated by both intracellular and extracellular Ca(2+), while the vesicle quantal size was mainly determined by extracellular Ca(2+) in chromaffin cells physiologically., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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8. Β-adrenergic-stimulated L-type channel Ca²+ entry mediates hypoxic Ca²+ overload in intact heart.
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Zhang H, Shang W, Zhang X, Gu J, Wang X, Zheng M, Wang Y, Zhou Z, Cao JM, Ji G, Zhang R, and Cheng H
- Subjects
- Animals, Cell Hypoxia, In Vitro Techniques, Male, Membrane Potential, Mitochondrial, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria metabolism, Models, Biological, Myocardium pathology, Calcium metabolism, Calcium Channels, L-Type metabolism, Calcium Signaling, Ion Channel Gating, Myocardium metabolism, Receptors, Adrenergic, beta metabolism
- Abstract
Ca(2+) mishandling plays a key role in ischemia- and hypoxia-related cardiac dysfunction and injury. However, the cellular and molecular mechanisms underlying hypoxic intracellular Ca(2+) ([Ca(2+)]i) overload remain incompletely understood. This study aimed to investigate possible mechanisms of [Ca(2+)]i overload during hypoxia in the intact heart. In Langendorff-perfused heart expressing the Ca(2+) indicator GCaMP2, confocal microscopy was used to simultaneously visualize [Ca(2+)]i, mitochondrial membrane potential (ΔΨm, by tetramethylrhodamine methyl ester) and sarcolemmal integrity (by Evans blue). Upon hypoxia (pO2 ~20 mmHg in glucose-free perfusate), [Ca(2+)]i transients were initially enhanced and then became depressed, arrhythmic, and completely abolished within 12 min. At ~20 min, basal [Ca(2+)]i rose to its first peak at a supraphysiological level, coincident with loss of ΔΨm and onset of rigor. A greater [Ca(2+)]i rise occurred at ~2h and was linked to the loss of sarcolemmal integrity. Removal of extracellular Ca(2+) or blockade of the l-type Ca(2+) channel (LTCC) (10 μM diltiazem or nifedipine) prevented [Ca(2+)]i overload and markedly delayed the loss of ΔΨm; by contrast, depletion of the sarcoplasmic reticulum Ca(2+) store by thapsigargin did not have any significant effect. Importantly, β-adrenergic blockade or depletion of the sympathetic catecholamine store by reserpine slowed the Ca(2+) and mitochondrial responses to hypoxia in intact heart. This LTCC-mediated hypoxic [Ca(2+)]i overload was reproduced in isolated cardiomyocytes when β-adrenergic agonist was present. Taken together, we conclude that Ca(2+) entry through β-adrenergic-stimulated LTCC underlies hypoxia-induced [Ca(2+)]i overload and the ensuing loss of mitochondrial function in intact heart., (© 2013. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2013
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9. Thiopental-induced insulin secretion via activation of IP3-sensitive calcium stores in rat pancreatic β-cells.
- Author
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Dou HQ, Xu YF, Sun JP, Shang S, Guo S, Zheng LH, Chen CC, Bruce IC, Yu X, and Zhou Z
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- Anesthetics, Intravenous, Animals, Boron Compounds pharmacology, Estrenes pharmacology, Glucose metabolism, Heparin pharmacology, Inositol 1,4,5-Trisphosphate antagonists & inhibitors, Inositol 1,4,5-Trisphosphate Receptors antagonists & inhibitors, Insulin analysis, Insulin Secretion, Insulin-Secreting Cells metabolism, Membrane Potentials drug effects, Patch-Clamp Techniques, Potassium Channels drug effects, Potassium Channels metabolism, Pyrrolidinones pharmacology, Rats, Rats, Wistar, Ryanodine pharmacology, Thapsigargin pharmacology, Calcium metabolism, Inositol 1,4,5-Trisphosphate metabolism, Inositol 1,4,5-Trisphosphate Receptors metabolism, Insulin metabolism, Insulin-Secreting Cells drug effects, Thiopental pharmacology
- Abstract
While glucose-stimulated insulin secretion depends on Ca(2+) influx through voltage-gated Ca(2+) channels in the cell membrane of the pancreatic β-cell, there is also ample evidence for an important role of intracellular Ca(2+) stores in insulin secretion, particularly in relation to drug stimuli. We report here that thiopental, a common anesthetic agent, triggers insulin secretion from the intact pancreas and primary cultured rat pancreatic β-cells. We investigated the underlying mechanisms by measurements of whole cell K(+) and Ca(2+) currents, membrane potential, cytoplasmic Ca(2+) concentration ([Ca(2+)](i)), and membrane capacitance. Thiopental-induced insulin secretion was first detected by enzyme-linked immunoassay, then further assessed by membrane capacitance measurement, which revealed kinetics distinct from glucose-induced insulin secretion. The thiopental-induced secretion was independent of cell membrane depolarization and closure of ATP-sensitive potassium (K(ATP)) channels. However, accompanied by the insulin secretion stimulated by thiopental, we recorded a significant intracellular [Ca(2+)] increase that was not from Ca(2+) influx across the cell membrane, but from intracellular Ca(2+) stores. The thiopental-induced [Ca(2+)](i) rise in β-cells was sensitive to thapsigargin, a blocker of the endoplasmic reticulum Ca(2+) pump, as well as to heparin (0.1 mg/ml) and 2-aminoethoxydiphenyl borate (2-APB; 100 μM), drugs that inhibit inositol 1,4,5-trisphosphate (IP(3)) binding to the IP(3) receptor, and to U-73122, a phospholipase C inhibitor, but insensitive to ryanodine. Thapsigargin also diminished thiopental-induced insulin secretion. Thus, we conclude that thiopental-induced insulin secretion is mediated by activation of the intracellular IP(3)-sensitive Ca(2+) store.
- Published
- 2012
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10. Action potential-triggered somatic exocytosis in mesencephalic trigeminal nucleus neurons in rat brain slices.
- Author
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Zhang B, Zhang XY, Luo PF, Huang W, Zhu FP, Liu T, Du YR, Wu QH, Lü J, Xiu Y, Liu LN, Huang HP, Guo S, Zheng H, Zhang CX, and Zhou Z
- Subjects
- Action Potentials physiology, Animals, In Vitro Techniques, Male, Rats, Rats, Sprague-Dawley, Calcium physiology, Exocytosis physiology, Neurons physiology, Trigeminal Nuclei physiology
- Abstract
The neurons in the mesencephalic trigeminal nucleus (MeV) play essential roles in proprioceptive sensation of the face and oral cavity. The somata of MeV neurons are generally assumed to carry out neuronal functions but not to play a direct role in synaptic transmission. Using whole-cell recording and membrane capacitance (C(m)) measurements, we found that the somata of MeV neurons underwent robust exocytosis (C(m) jumps) upon depolarization and with the normal firing of action potentials in brain slices. Both removing [Ca(2+)](o) and buffering [Ca(2+)](i) with BAPTA blocked this exocytosis, indicating that it was completely Ca(2+) dependent. In addition, an electron microscopic study showed synaptic-like vesicles approximated to the plasma membrane in somata. There was a single Ca(2+)-dependent releasable vesicle pool with a peak release rate of 1912 fF s(-1). Importantly, following depolarization-induced somatic exocytosis, GABA-mediated postsynaptic currents were transiently reduced by 31%, suggesting that the somatic vesicular release had a retrograde effect on afferent GABAergic transmission. These results provide strong evidence that the somata of MeV neurons undergo robust somatic secretion and may play a crucial role in bidirectional communication between somata and their synaptic inputs in the central nervous system.
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- 2012
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11. Calcium triggers exocytosis from two types of organelles in a single astrocyte.
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Liu T, Sun L, Xiong Y, Shang S, Guo N, Teng S, Wang Y, Liu B, Wang C, Wang L, Zheng L, Zhang CX, Han W, and Zhou Z
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- Animals, Calcium Signaling drug effects, Calcium Signaling physiology, Cells, Cultured, Exocytosis physiology, Glial Fibrillary Acidic Protein, Glutamic Acid metabolism, Green Fluorescent Proteins genetics, Hippocampus cytology, Humans, Lysosomal-Associated Membrane Protein 1 metabolism, Lysosomes drug effects, Mice, Mice, Inbred C57BL, Mutation genetics, Neurotoxins pharmacology, Receptors, Glutamate genetics, Tetanus Toxin pharmacology, Transfection methods, Transport Vesicles drug effects, Vesicle-Associated Membrane Protein 2 genetics, Vesicle-Associated Membrane Protein 2 metabolism, Vesicle-Associated Membrane Protein 3 metabolism, Vesicular Glutamate Transport Protein 1 genetics, Astrocytes ultrastructure, Calcium metabolism, Exocytosis drug effects, Lysosomes metabolism, Transport Vesicles metabolism
- Abstract
Astrocytes release a variety of signaling molecules including glutamate, D-serine, and ATP in a regulated manner. Although the functions of these molecules, from regulating synaptic transmission to controlling specific behavior, are well documented, the identity of their cellular compartment(s) is still unclear. Here we set out to study vesicular exocytosis and glutamate release in mouse hippocampal astrocytes. We found that small vesicles and lysosomes coexisted in the same freshly isolated or cultured astrocytes. Both small vesicles and lysosome fused with the plasma membrane in the same astrocytes in a Ca(2+)-regulated manner, although small vesicles were exocytosed more efficiently than lysosomes. Blockade of the vesicle glutamate transporter or cleavage of synaptobrevin 2 and cellubrevin (both are vesicle-associated membrane proteins) with a clostridial toxin greatly inhibited glutamate release from astrocytes, while lysosome exocytosis remained intact. Thus, both small vesicles and lysosomes contribute to Ca(2+)-dependent vesicular exocytosis, and small vesicles support glutamate release from astrocytes.
- Published
- 2011
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12. An inhibitory effect of extracellular Ca2+ on Ca2+-dependent exocytosis.
- Author
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Xiong W, Liu T, Wang Y, Chen X, Sun L, Guo N, Zheng H, Zheng L, Ruat M, Han W, Zhang CX, and Zhou Z
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- Animals, Caffeine pharmacology, Calcimimetic Agents pharmacology, Cell Membrane drug effects, Cell Membrane metabolism, Chromaffin Cells cytology, Chromaffin Cells drug effects, Chromaffin Cells metabolism, Extracellular Space drug effects, Ganglia, Spinal cytology, Neurons cytology, Neurons drug effects, Neurons metabolism, Photolysis, Rats, Rats, Wistar, Calcium metabolism, Exocytosis drug effects, Extracellular Space metabolism
- Abstract
Aim: Neurotransmitter release is elicited by an elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)). The action potential triggers Ca(2+) influx through Ca(2+) channels which causes local changes of [Ca(2+)](i) for vesicle release. However, any direct role of extracellular Ca(2+) (besides Ca(2+) influx) on Ca(2+)-dependent exocytosis remains elusive. Here we set out to investigate this possibility on rat dorsal root ganglion (DRG) neurons and chromaffin cells, widely used models for studying vesicle exocytosis., Results: Using photolysis of caged Ca(2+) and caffeine-induced release of stored Ca(2+), we found that extracellular Ca(2+) inhibited exocytosis following moderate [Ca(2+)](i) rises (2-3 µM). The IC(50) for extracellular Ca(2+) inhibition of exocytosis (ECIE) was 1.38 mM and a physiological reduction (∼30%) of extracellular Ca(2+) concentration ([Ca(2+)](o)) significantly increased the evoked exocytosis. At the single vesicle level, quantal size and release frequency were also altered by physiological [Ca(2+)](o). The calcimimetics Mg(2+), Cd(2+), G418, and neomycin all inhibited exocytosis. The extracellular Ca(2+)-sensing receptor (CaSR) was not involved because specific drugs and knockdown of CaSR in DRG neurons did not affect ECIE., Conclusion/significance: As an extension of the classic Ca(2+) hypothesis of synaptic release, physiological levels of extracellular Ca(2+) play dual roles in evoked exocytosis by providing a source of Ca(2+) influx, and by directly regulating quantal size and release probability in neuronal cells.
- Published
- 2011
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13. Interleukin-6 increases intracellular Ca2+ concentration and induces catecholamine secretion in rat carotid body glomus cells.
- Author
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Fan J, Zhang B, Shu HF, Zhang XY, Wang X, Kuang F, Liu L, Peng ZW, Wu R, Zhou Z, and Wang BR
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- Adenosine Triphosphate metabolism, Animals, Cadmium pharmacology, Calcium Signaling drug effects, Calcium Signaling physiology, Carotid Body drug effects, Chemoreceptor Cells drug effects, Interleukin-1 metabolism, Interleukin-1 pharmacology, Interleukin-6 pharmacology, Intracellular Fluid metabolism, Male, Neuroimmunomodulation drug effects, Neuroimmunomodulation physiology, Rats, Receptors, Interleukin-1 drug effects, Receptors, Interleukin-1 metabolism, Receptors, Interleukin-6 drug effects, Receptors, Interleukin-6 metabolism, Up-Regulation drug effects, Up-Regulation physiology, Calcium metabolism, Carotid Body metabolism, Catecholamines metabolism, Chemoreceptor Cells metabolism, Interleukin-6 metabolism
- Abstract
Although abundant evidence indicates mutual regulation between the immune and the central nervous systems, how the immune signals are transmitted to the brain is still an unresolved question. In a previous study we found strong expression of proinflammatory cytokine receptors, including interleukin (IL)-1 receptor I and IL-6 receptor alpha in the rat carotid body (CB), a well-known arterial chemoreceptor that senses a variety of chemostimuli in the arterial blood. We demonstrated that IL-1 stimulation increases intracellular calcium ([Ca(2+)](i)) in CB glomus cells, releases ATP, and increases the discharge rate in carotid sinus nerve. To explore the effect of IL-6 on CB, here we examine the effect of IL-6 on [Ca(2+)](i) and catecholamine (CA) secretion in rat CB glomus cells. Calcium imaging showed that extracellular application of IL-6 induced a rise in [Ca(2+)](i) in cultured glomus cells. Amperometry showed that local application of IL-6 evoked CA release from glomus cells. Furthermore, the CA secretory response to IL-6 was blocked by 200 microM Cd(2+), a well-known Ca(2+) channel blocker. Our experiments provide further evidence for the responsiveness of the CB to proinflammatory cytokines and indicate that the CB might play a role in inflammation sensing and transmission of such information to the brain.
- Published
- 2009
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14. Electrical activity and exocytotic correlates of biphasic insulin secretion from beta-cells of canine islets of Langerhans: contribution of tuning two modes of Ca2+ entry-dependent exocytosis to two modes of glucose-induced electrical activity.
- Author
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Misler S, Zhou Z, Dickey AS, Silva AM, Pressel DM, and Barnett DW
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- Animals, Calcium Channels metabolism, Cells, Cultured, Dogs, Glucose metabolism, Insulin Secretion, Insulin-Secreting Cells cytology, Calcium metabolism, Exocytosis physiology, Insulin metabolism, Insulin-Secreting Cells metabolism, Membrane Potentials physiology, Secretory Vesicles metabolism
- Abstract
Biphasic insulin secretion in response to glucose, consisting of a transient first phase followed by a progressive second phase, is well described in pancreatic islets. Using single canine beta-cells we have compared the time courses of electrical activity and insulin granule exocytosis to biphasic insulin secretion. Short trains of action potentials, similar those found during first phase insulin secretion, trigger phasic exocytosis from a small pool of insulin granules, likely an immediately releasable pool docked near voltage activated Ca(2+) channels. In contrast, plateau depolarizations to between -35 and -20 mV resembling those during second phase insulin secretion, trigger tonic exocytosis from a larger pool of insulin granules, likely a highly Ca(2+)-sensitive pool farther from Ca(2+) channels. Both phasic and tonic modes of exocytosis are enhanced by glucose, via its metabolism. Hence, in canine beta-cells two distinct components of exocytosis, tuned to two components of electrical activity, may contribute significantly to biphasic insulin secretion.
- Published
- 2009
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15. Action potential modulates Ca2+-dependent and Ca2+-independent secretion in a sensory neuron.
- Author
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Zheng H, Fan J, Xiong W, Zhang C, Wang XB, Liu T, Liu HJ, Sun L, Wang YS, Zheng LH, Wang BR, Zhang CX, and Zhou Z
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- Animals, Cell Membrane physiology, Cells, Cultured, Electric Capacitance, Endocytosis, Excitatory Postsynaptic Potentials, In Vitro Techniques, Kinetics, Patch-Clamp Techniques, Photolysis, Rats, Rats, Wistar, Action Potentials, Calcium metabolism, Ganglia, Spinal physiology, Neurotransmitter Agents metabolism, Sensory Receptor Cells metabolism
- Abstract
Neurotransmitter release normally requires calcium triggering. However, the somata of dorsal root ganglion (DRG) neurons possess a calcium-independent but voltage-dependent secretion (CIVDS) in addition to the classic calcium-dependent secretion (CDS). Here, we investigated the physiological role of CIVDS and the contributions of CIVDS and CDS induced by action potentials (APs) in DRG soma. Using membrane capacitance measurements, caged calcium photolysis, and membrane capacitance kinetics analysis, we demonstrated that AP-induced secretion had both CIVDS and CDS components. Following physiological stimuli, the dominant component of AP-induced secretion was either CIVDS for spontaneous firing or CDS for high-intensity stimuli. AP frequency modulates CDS-coupled exocytosis and CIVDS-coupled endocytosis but not CIVDS-coupled exocytosis and CDS-coupled endocytosis. Finally, CIVDS did not contribute to excitatory postsynaptic currents induced by APs in DRG presynaptic terminals in the spinal cord. Thus, CIVDS is probably an essential physiological component of AP-induced secretion in the soma. These findings bring novel insights into primary sensory processes in DRG neurons.
- Published
- 2009
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16. IL-1beta inhibits IK and increases [Ca2+]i in the carotid body glomus cells and increases carotid sinus nerve firings in the rat.
- Author
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Shu HF, Wang BR, Wang SR, Yao W, Huang HP, Zhou Z, Wang X, Fan J, Wang T, and Ju G
- Subjects
- Action Potentials physiology, Animals, Dose-Response Relationship, Drug, Drug Interactions, Interleukin 1 Receptor Antagonist Protein pharmacology, Male, Neurons physiology, Patch-Clamp Techniques methods, Potassium Channels drug effects, Rats, Rats, Sprague-Dawley, Action Potentials drug effects, Calcium metabolism, Carotid Body cytology, Carotid Sinus innervation, Interleukin-1beta pharmacology, Neurons drug effects, Potassium Channels physiology
- Abstract
Increasing evidence indicates that there exists a reciprocal communication between the immune system and the brain. Interleukin 1beta (IL-1beta), a proinflammatory cytokine produced during immune challenge, is believed to be one of the mediators of immune-to-brain communication, but how it gets into the brain is unknown because of its large molecular weight and difficulty in crossing the blood-brain barrier. Our previous work has demonstrated that IL-1 receptor type I is strongly expressed in the glomus cells of rat carotid body (CB), a well characterized polymodal chemoreceptive organ which serves not only for the detection of hypoxia, hypercapnia and acidity, but also for low temperature and blood glucose. The present study was designed to test whether IL-1beta could stimulate the CB glomus cells and alter the discharge properties in the carotid sinus nerve, the afferent nerve innervating the organ. The results from whole-cell patch-clamp recordings and calcium imaging showed that extracellular application of IL-1beta significantly decreased the outward potassium current and triggered a transient rise in [Ca(2+)](i) in the cultured glomus cells of rat CB. Furthermore, by using extracellular recordings and pharmacological intervention, it was found that IL-1beta stimulation of the CB in the anaesthetized rat in vivo significantly increased the discharge rate in the carotid sinus nerve, most probably mediated by ATP release. This experiment provides evidence that the CB responds to cytokine stimulation and proposes the possibility that the CB might play a role in immune-to-brain communication.
- Published
- 2007
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17. Calcium influx through If channels in rat ventricular myocytes.
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Yu X, Chen XW, Zhou P, Yao L, Liu T, Zhang B, Li Y, Zheng H, Zheng LH, Zhang CX, Bruce I, Ge JB, Wang SQ, Hu ZA, Yu HG, and Zhou Z
- Subjects
- Animals, Cells, Cultured, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Rats, Rats, Inbred SHR, Rats, Sprague-Dawley, Rats, Wistar, Calcium metabolism, Calcium Signaling physiology, Ion Channel Gating physiology, Ion Channels metabolism, Myocytes, Cardiac physiology, Potassium Channels metabolism, Ventricular Function
- Abstract
The hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, or cardiac (I(f))/neuronal (I(h)) time- and voltage-dependent inward cation current channels, are conventionally considered as monovalent-selective channels. Recently we discovered that calcium ions can permeate through HCN4 and I(h) channels in neurons. This raises the possibility of Ca(2+) permeation in I(f), the I(h) counterpart in cardiac myocytes, because of their structural homology. We performed simultaneous measurement of fura-2 Ca(2+) signals and whole cell currents produced by HCN2 and HCN4 channels (the 2 cardiac isoforms present in ventricles) expressed in HEK293 cells and by I(f) in rat ventricular myocytes. We observed Ca(2+) influx when HCN/I(f) channels were activated. Ca(2+) influx was increased with stronger hyperpolarization or longer pulse duration. Cesium, an I(f) channel blocker, inhibited I(f) and Ca(2+) influx at the same time. Quantitative analysis revealed that Ca(2+) flux contributed to approximately 0.5% of current produced by the HCN2 channel or I(f). The associated increase in Ca(2+) influx was also observed in spontaneously hypertensive rat (SHR) myocytes in which I(f) current density is higher than that of normotensive rat ventricle. In the absence of EGTA (a Ca(2+) chelator), preactivation of I(f) channels significantly reduced the action potential duration, and the effect was blocked by another selective I(f) channel blocker, ZD-7288. In the presence of EGTA, however, preactivation of I(f) channels had no effects on action potential duration. Our data extend our previous discovery of Ca(2+) influx in I(h) channels in neurons to I(f) channels in cardiac myocytes.
- Published
- 2007
- Full Text
- View/download PDF
18. Ca2+ sparks and Ca2+ glows in superior cervical ganglion neurons.
- Author
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Yao LJ, Wang G, Ou-Yang KF, Wei CL, Wang XH, Wang SR, Yao W, Huang HP, Luo JH, Wu CH, Liu J, Zhou Z, and Cheng HP
- Subjects
- Animals, Animals, Newborn, Caffeine antagonists & inhibitors, Cells, Cultured, Neurons metabolism, Rats, Superior Cervical Ganglion cytology, Thapsigargin pharmacology, Calcium metabolism, Calcium Signaling drug effects, Endoplasmic Reticulum metabolism, Superior Cervical Ganglion metabolism
- Abstract
Aim: Ca2+ release from the endoplasmic reticulum (ER) is an integral component of neuronal Ca2+ signaling. The present study is to investigate properties of local Ca2+ release events in superior cervical ganglion (SCG) neurons., Methods: Primary cultured SCG neurons were prepared from neonatal rats (P3-P7). Low concentration of caffeine was used to induce Ca2+ release from the ER Ca2+ store, and intracellular Ca2+ was recorded by high-resolution line scan confocal imaging and the Ca2+ indicator Fluo-4., Results: Two populations of local Ca2+ release events with distinct temporal characteristics were evoked by 1.5 mmol/L caffeine near the surface membrane in the soma and the neurites of SCG neurons. Brief events similar to classic Ca2+ sparks lasted a few hundreds of milliseconds, whereas long-lasting events displayed duration up to tens of seconds. Typical somatic and neurite sparks were of 0.3- and 0.52-fold increase in local Fluo-4 fluorescence, respectively. Typical Ca2+ glows were brighter (deltaF/F0 approximately 0.6), but were highly confined in space. The half maximum of full duration of neurite sparks was much longer than those in the soma (685 vs 381 ms)., Conclusion: Co-existence of Ca2+ sparks and Ca2+ glows in SCG neurons indicates distinctive local regulation of Ca2+ release kinetics. The local Ca2+ signals of variable, site-specific temporal length may bear important implications in encoding a 'memory' of the trigger signal.
- Published
- 2006
- Full Text
- View/download PDF
19. A simulation study on the Ca2+-independent but voltage-dependent exocytosis and endocytosis in dorsal root ganglion neurons.
- Author
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Yang H, Zhang C, Zheng H, Xiong W, Zhou Z, Xu T, and Ding JP
- Subjects
- Animals, Cell Membrane physiology, Cells, Cultured, Computer Simulation, Neurotransmitter Agents metabolism, Rats, Rats, Wistar, Synaptic Transmission physiology, Calcium metabolism, Endocytosis physiology, Exocytosis physiology, Ganglia, Spinal physiology, Membrane Potentials physiology, Models, Neurological, Neurons physiology
- Abstract
In patch-clamped somata of dorsal root ganglion (DRG) neurons, two types of secretion have been proposed: Ca(2+)-dependent secretion and Ca(2+)-independent but voltage-dependent secretion (CIVDS). The Ca(2+)-induced and the depolarization-induced membrane capacitance (C(m)) increases contribute 80 and 20% to the total C(m) increase, respectively (Zhang and Zhou in Nat Neurosci 5:425, 2002). In order to explore the mechanism of the voltage-dependent C(m) change (DeltaC(m)), we constructed a model with sequential states. The simulation with this model closely approximates all the experimental data. The model predicts that the majority of fusion events (approximately 80%) are so-called "kiss-and-run" events, which account for the fast recovery or the rapid retrieval feature of the signals. The remaining 20% are attributed to full fusion events, which account for a slow retrieval feature. On the basis of the model, one mechanism of the activity-dependent endocytosis has revealed a differential distribution of vesicles between the kiss-and-run and full fusion states at different stimulation frequencies. The quantitative model presented in this study may help us to understand the mechanism of the CIVDS and the tightly coupled endocytosis found in mammalian DRG neurons.
- Published
- 2005
- Full Text
- View/download PDF
20. Ca2+ sparks and secretion in dorsal root ganglion neurons.
- Author
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Ouyang K, Zheng H, Qin X, Zhang C, Yang D, Wang X, Wu C, Zhou Z, and Cheng H
- Subjects
- Animals, Caffeine pharmacology, Calcitonin Gene-Related Peptide, Exocytosis drug effects, Exocytosis physiology, Ganglia, Spinal metabolism, Patch-Clamp Techniques, Rats, Theobromine analogs & derivatives, Theobromine pharmacology, Calcium metabolism, Endoplasmic Reticulum metabolism, Ganglia, Spinal cytology, Neurons, Afferent metabolism, Ryanodine Receptor Calcium Release Channel metabolism, Signal Transduction physiology
- Abstract
Ca(2+) sparks as the elementary intracellular Ca(2+) release events are instrumental to local control of Ca(2+) signaling in many types of cells. Here, we visualized neural Ca(2+) sparks in dorsal root ganglion (DRG) sensory neurons and investigated possible role of DRG sparks in the regulation of secretion from the somata of the cell. DRG sparks arose mainly from type 3 ryanodine receptor Ca(2+) release channels on subsurface cisternae of the endoplasmic reticulum, rendering a striking subsurface localization. Caffeine- or 3,7-dimethyl-1-(2-propynyl)xanthine-induced store Ca(2+) release, in the form of Ca(2+) sparks, triggered exocytosis, independently of membrane depolarization and external Ca(2+). The spark-secretion coupling probability was estimated to be between 1 vesicle per 6.6 sparks and 1 vesicle per 11.4 sparks. During excitation, subsurface sparks were evoked by physiological Ca(2+) entry via the Ca(2+)-induced Ca(2+) release mechanism, and their synergistic interaction with Ca(2+) influx accounted for approximately 60% of the Ca(2+)-dependent exocytosis. Furthermore, inhibition of Ca(2+)-induced Ca(2+) release abolished endotoxin-induced secretion of pain-related neuropeptides. These findings underscore an important role for Ca(2+) sparks in the amplification of surface Ca(2+) influx and regulation of neural secretion.
- Published
- 2005
- Full Text
- View/download PDF
21. Calcium- and dynamin-independent endocytosis in dorsal root ganglion neurons.
- Author
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Zhang C, Xiong W, Zheng H, Wang L, Lu B, and Zhou Z
- Subjects
- Action Potentials drug effects, Action Potentials physiology, Animals, Calcium pharmacology, Cells, Cultured, Dynamins pharmacology, Endocytosis drug effects, Ganglia, Spinal drug effects, Neurons drug effects, Rats, Rats, Wistar, Calcium physiology, Dynamins physiology, Endocytosis physiology, Ganglia, Spinal physiology, Neurons physiology
- Abstract
Synaptic vesicle endocytosis is believed to require calcium and the GTPase dynamin. We now report a form of rapid endocytosis (RE) in dorsal root ganglion (DRG) neurons that, unlike previously described forms of endocytosis, is independent of calcium and dynamin. The RE is tightly coupled to calcium-independent but voltage-dependent secretion (CIVDS). Using FM dye and capacitance measurements, we show that membrane depolarization induces RE in the absence of calcium. Inhibition of dynamin function does not affect RE. The magnitude of RE is proportional to that of preceding CIVDS and stimulation frequency. Inhibitors of protein kinase A (PKA) suppress RE induced by high-frequency depolarization, while PKA activators enhance RE induced by low-frequency depolarization. Biochemical experiments demonstrate that depolarization directly upregulates PKA activity in calcium-free medium. These results reveal a calcium- and dynamin-independent form of endocytosis, which is controlled by neuronal activity and PKA-dependent phosphorylation, in DRG neurons.
- Published
- 2004
- Full Text
- View/download PDF
22. Calcium influx through hyperpolarization-activated cation channels (I(h) channels) contributes to activity-evoked neuronal secretion.
- Author
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Yu X, Duan KL, Shang CF, Yu HG, and Zhou Z
- Subjects
- Animals, Cell Line, Humans, Long-Term Potentiation, Neurons physiology, Patch-Clamp Techniques, Rats, Rats, Wistar, Spectrometry, Fluorescence, Calcium metabolism, Ion Channels metabolism, Neurons metabolism
- Abstract
The hyperpolarization-activated cation channels (I(h)) play a distinct role in rhythmic activities in a variety of tissues, including neurons and cardiac cells. In the present study, we investigated whether Ca(2+) can permeate through the hyperpolarization-activated pacemaker channels (HCN) expressed in HEK293 cells and I(h) channels in dorsal root ganglion (DRG) neurons. Using combined measurements of whole-cell currents and fura-2 Ca(2+) imaging, we found that there is a Ca(2+) influx in proportion to I(h) induced by hyperpolarization in HEK293 cells. The I(h) channel blockers Cs(+) and ZD7288 inhibit both HCN current and Ca(2+) influx. Measurements of the fractional Ca(2+) current showed that it constitutes 0.60 +/- 0.02% of the net inward current through HCN4 at -120 mV. This fractional current is similar to that of the low Ca(2+)-permeable AMPA-R (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) channels in Purkinje neurons. In DRG neurons, activation of I(h) for 30 s also resulted in a Ca(2+) influx and an elevated action potential-induced secretion, as assayed by the increase in membrane capacitance. These results suggest a functional significance for I(h) channels in modulating neuronal secretion by permitting Ca(2+) influx at negative membrane potentials.
- Published
- 2004
- Full Text
- View/download PDF
23. Time course of action of antagonists of mitochondrial Ca uptake in intact ventricular myocytes.
- Author
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Zhou Z and Bers DM
- Subjects
- Animals, Calcium Channel Blockers pharmacology, Carbonyl Cyanide m-Chlorophenyl Hydrazone pharmacology, Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone pharmacology, Ferrets, Heart Ventricles, Ionophores pharmacology, Mitochondria, Heart drug effects, Ruthenium Compounds pharmacology, Ruthenium Red pharmacology, Time Factors, Calcium metabolism, Mitochondria, Heart metabolism, Myocytes, Cardiac metabolism
- Abstract
Mitochondrial Ca uptake is important for ATP production and intracellular Ca buffering. Several agents are often used to interfere with mitochondrial Ca transport, but the use of these agents in intact cells is complicated by lack of knowledge about how rapidly these agents gain access to intracellular mitochondria. We have developed a novel method to assess the time course with which extracellularly applied inhibitors gain access to mitochondria in intact ventricular myocytes preloaded with the fluorescent Ca indicator indo-1-AM. Cell contraction (assessed as the normalized change in cell length delta L(n)) was employed as an index of the cytosolic [Ca] ([Ca](c)), and was compared with the indo-l ratio R(n), which reflects both mitochondrial [Ca] ([Ca](m)) and [Ca](c). Upon abrupt plasma membrane damage in control cells, the delay ( t(k)) between the rise in L(n)and R(n) was <10 s (reflecting the time lag between the change in [Ca](c) and that in [Ca](m)). Exposure of cells to 50 microM ruthenium red (RR) increased t(k) as a monotonic function of preincubation time. In contrast, 10 microM Ru360, a selective and more potent Ca uniporter blocker ( K(i) approximately 0.2 nM) reached a comparable maximal t(k) after only 10 min, making it practical to use in intact cells. Carbonylcyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) and carbonylcyanide m-chlorophenylhydrazone (CCCP) produced smaller maximal effects on t(k), but did so almost immediately. These results are the first quantitative data on the time course of blockade of mitochondrial Ca uptake by the four most widely used mitochondrial Ca uptake antagonists in single ventricular myocytes.
- Published
- 2002
- Full Text
- View/download PDF
24. Calcium Influx through Hyperpolarization-Activated Cation Channels (I h Channels) Contributes to Activity-Evoked Neuronal Secretion
- Author
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Yu, Xiao, Duan, Kai-Lai, Shang, Chun-Feng, Yu, Han-Gang, and Zhou, Zhuan
- Published
- 2004
25. Stretch‐induced Ca2+ independent ATP release in hippocampal astrocytes
- Author
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Xiong, Yingfei, Teng, Sasa, Zheng, Lianghong, Sun, Suhua, Li, Jie, Guo, Ning, Li, Mingli, Wang, Li, Zhu, Feipeng, Wang, Changhe, Rao, Zhiren, and Zhou, Zhuan
- Subjects
Male ,Mice, Knockout ,Glutamic Acid ,Mice, Transgenic ,Hippocampus ,Synaptic Transmission ,Exocytosis ,Rats ,Rats, Sprague-Dawley ,Mice ,Adenosine Triphosphate ,Astrocytes ,Animals ,Inositol 1,4,5-Trisphosphate Receptors ,Calcium ,Female ,Receptors, Purinergic P2X7 ,Stress, Mechanical ,Cells, Cultured ,Neuroscience - Abstract
KEY POINTS: Similar to neurons, astrocytes actively participate in synaptic transmission via releasing gliotransmitters. The Ca(2+)‐dependent release of gliotransmitters includes glutamate and ATP. Following an ‘on‐cell‐like’ mechanical stimulus to a single astrocyte, Ca(2+) independent single, large, non‐quantal, ATP release occurs. Astrocytic ATP release is inhibited by either selective antagonist treatment or genetic knockdown of P2X7 receptor channels. Our work suggests that ATP can be released from astrocytes via two independent pathways in hippocampal astrocytes; in addition to the known Ca(2+)‐dependent vesicular release, larger non‐quantal ATP release depends on P2X7 channels following mechanical stretch. ABSTRACT: Astrocytic ATP release is essential for brain functions such as synaptic long‐term potentiation for learning and memory. However, whether and how ATP is released via exocytosis remains hotly debated. All previous studies of non‐vesicular ATP release have used indirect assays. By contrast, two recent studies report vesicular ATP release using more direct assays. In the present study, using patch clamped ‘ATP‐sniffer cells’, we re‐investigated astrocytic ATP release at single‐vesicle resolution in hippocampal astrocytes. Following an ‘on‐cell‐like’ mechanical stimulus of a single astrocyte, a Ca(2+) independent single large non‐quantal ATP release occurred, in contrast to the Ca(2+)‐dependent multiple small quantal ATP release in a chromaffin cell. The mechanical stimulation‐induced ATP release from an astrocyte was inhibited by either exposure to a selective antagonist or genetic knockdown of P2X7 receptor channels. Functional P2X7 channels were expressed in astrocytes in hippocampal brain slices. Thus, in addition to small quantal ATP release, larger non‐quantal ATP release depends on P2X7 channels in astrocytes.
- Published
- 2018
26. Ca2+-Dependent and Ca2+-Independent ATP Release in Astrocytes.
- Author
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Xiong, Yingfei, Sun, Suhua, Teng, Sasa, Jin, Mu, and Zhou, Zhuan
- Subjects
ASTROCYTES ,ADENOSINE triphosphate ,DISEASES - Published
- 2018
- Full Text
- View/download PDF
27. Time course of action of antagonists of mitochondrial Ca uptake in intact ventricular myocytes.
- Author
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Zhou, Zhuan and Bers, Donald M.
- Subjects
MUSCLE cells ,MITOCHONDRIA ,CALCIUM ,ORGANELLES ,CELLS ,TIME - Abstract
Mitochondrial Ca uptake is important for ATP production and intracellular Ca buffering. Several agents are often used to interfere with mitochondrial Ca transport, but the use of these agents in intact cells is complicated by lack of knowledge about how rapidly these agents gain access to intracellular mitochondria. We have developed a novel method to assess the time course with which extracellularly applied inhibitors gain access to mitochondria in intact ventricular myocytes preloaded with the fluorescent Ca indicator indo-1-AM. Cell contraction (assessed as the normalized change in cell length ΔL
n ) was employed as an index of the cytosolic [Ca] ([Ca]c ), and was compared with the indo-l ratio Rn , which reflects both mitochondrial [Ca] ([Ca]m ) and [Ca]c . Upon abrupt plasma membrane damage in control cells, the delay (tk ) between the rise in Ln and Rn was <10 s (reflecting the time lag between the change in [Ca]c and that in [Ca]m ). Exposure of cells to 50 µM ruthenium red (RR) increased tk as a monotonic function of preincubation time. In contrast, 10 µM Ru360, a selective and more potent Ca uniporter blocker (Ki ~0.2 nM) reached a comparable maximal tk after only 10 min, making it practical to use in intact cells. Carbonylcyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) and carbonylcyanide m-chlorophenylhydrazone (CCCP) produced smaller maximal effects on tk , but did so almost immediately. These results are the first quantitative data on the time course of blockade of mitochondrial Ca uptake by the four most widely used mitochondrial Ca uptake antagonists in single ventricular myocytes. [ABSTRACT FROM AUTHOR]- Published
- 2002
- Full Text
- View/download PDF
28. Astrocytic Piezo1-mediated mechanotransduction determines adult neurogenesis and cognitive functions.
- Author
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Chi, Shaopeng, Cui, Yaxiong, Wang, Haiping, Jiang, Jinghui, Zhang, Tingxin, Sun, Suhua, Zhou, Zhuan, Zhong, Yi, and Xiao, Bailong
- Subjects
- *
COGNITIVE ability , *NEUROGENESIS , *NEURAL stem cells , *LONG-term potentiation , *BRAIN anatomy - Abstract
Adult brain activities are generally believed to be dominated by chemical and electrical transduction mechanisms. However, the importance of mechanotransduction mediated by mechano-gated ion channels in brain functions is less appreciated. Here, we show that the mechano-gated Piezo1 channel is expressed in the exploratory processes of astrocytes and utilizes its mechanosensitivity to mediate mechanically evoked Ca2+ responses and ATP release, establishing Piezo1-mediated mechano-chemo transduction in astrocytes. Piezo1 deletion in astrocytes causes a striking reduction of hippocampal volume and brain weight and severely impaired (but ATP-rescuable) adult neurogenesis in vivo , and it abolishes ATP-dependent potentiation of neural stem cell (NSC) proliferation in vitro. Piezo1-deficient mice show impaired hippocampal long-term potentiation (LTP) and learning and memory behaviors. By contrast, overexpression of Piezo1 in astrocytes sufficiently enhances mechanotransduction, LTP, and learning and memory performance. Thus, astrocytes utilize Piezo1-mediated mechanotransduction mechanisms to robustly regulate adult neurogenesis and cognitive functions, conceptually highlighting the importance of mechanotransduction in brain structure and function. [Display omitted] • Piezo1 mediates mechanically evoked Ca2+ responses and ATP release in astrocytes • Astrocytic deletion of Piezo reduces hippocampal volume and brain weight • Astrocytic Piezo1 affects ATP-dependent adult neurogenesis in vivo and in vitro • Astrocytic Piezo1 is necessary and sufficient in promoting LTP and learning and memory Chi et al. find that astrocytes utilize the specialized mechanosensor Piezo1 to convert mechanical forces into Ca2+ and ATP signaling, which regulates adult neurogenesis and cognitive functions, conceptually highlighting the importance of mechanotransduction in brain structure and function. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
29. Glucose-induced Ca[sup2+] signals in rat pancreatic β cells.
- Author
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Lou Xuelin, Zeng Xuhui, Qu Anlian, and Zhou Zhuan
- Subjects
- *
GLUCOSE , *OSCILLATING chemical reactions , *CALCIUM , *ABSORPTION - Abstract
Studies the influences of varied factors on glucose-induced glucose-induced-decrease-plateau (GIDP) and calcium oscillation. Mechanism of glucose-induced internal calcium release; Identification of calcium channels in the glucose-induced calcium signals; Characterization of calcium signals in rat pancreatic beta cells.
- Published
- 2001
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