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In recent years, electroceuticals have been spotlighted as an emerging treatment for various severe chronic brain diseases, owing to their intrinsic advantage of electrical interaction with the brain, which is the most electrically active organ. However, the majority of research has verified only the short-term efficacy through acute studies in laboratory tests owing to the lack of a reliable miniaturized platform for long-term animal studies. The construction of a sufficient integrated system for such a platform is extremely difficult because it requires multi-disciplinary work using state-of-the-art technologies in a wide range of fields. In this study, we propose a complete system of an implantable platform for long-term preclinical brain studies. Our proposed system, the extra-cranial brain activator (ECBA), consists of a titanium-packaged implantable module and a helmet-type base station that powers the module wirelessly. The ECBA can also be controlled by a remote handheld device. Using the ECBA, we performed a long-term non-anesthetic study with multiple canine subjects, and the resulting PET-CT scans demonstrated remarkable enhancement in brain activity relating to memory and sensory skills. Furthermore, the histological analysis and high-temperature aging test confirmed the reliability of the system for up to 31 months. Hence, the proposed ECBA system is expected to lead a new paradigm of human neuromodulation studies in the near future.

Introduction Patients with repaired tetralogy of Fallot (rTF) and severe pulmonary regurgitation frequently progress to dilation and dysfunction of the right ventricle (RV). It has been documented in the literature that there is a correlation between the duration of the QRS in the surface electrocardiogram and the hemodynamic parameters of the RV of these patients, suggesting the presence of a mechanical-electrical interaction. Purpose To determine if there is an association between the contraction delay in certain areas of the RV measured in M-mode echocardiography and the delay in electrical activation measured in the electroanatomic map (EAM) of RV in patients with rTF. Methods Unicentric and observational study of all patients with rTF undergoing EAM, echocardiography with study of RV asynchrony and cardiac magnetic resonance imaging (MRI). Activation delay in the antero-basal area and in the RV outflow tract (RVOT) in the EAM were both analysed (Figure 1A). The shortening delay in the same areas in M-mode echocardiography was also evaluated (Figure 1B, C). MRI data regarding volume and ejection fraction was also collected. Results 64 patients were included (36.7±10.6 years, 65% men). The mean total activation time of the RV (RV-TAT) was 127.3±42.4 ms. Activation mapping showed a recurrent pattern with beginning in the interventricular septum and ending in RV antero-basal region and/or RVOT. A linear positive correlation was observed between RV-TAT and the activation delay in both regions analysed (ρ=0.60 and ρ=0.52, respectively; p Conclusions There is a mechanical-electrical interaction in the RV of patients with rTF, with a negative correlation between the activation delay and RVEF and between mechanical and electrical activation delay in specific anatomical regions (regional mechanical-electrical interaction). These results may guide future studies on resynchronization in this heart disease. Figure 1. EAM and echocardiographic measures Funding Acknowledgement Type of funding source: None

Cardiac fibroblasts are widely represented in mammalian cardiac tissue. These cells are connected with cardiomyocytes by gap junctions and they have own changeable membrane potential, so that fibroblasts can influence cardiomyocyte electrical activity. This effect may be analyzed in mathematical models. Existing mathematical models of fibroblast-cardiomyocyte interaction allow anyone to study only electrical responses of the cardiomyocytes and fibroblasts to their electrical interaction. In our work we have considered the fibroblast influence on the cardiomyocytes mechanics. In numerical experiments we reveal significant changes in the cardiomyocyte action potential duration and force depending on the number of fibroblast connected with the cardiomyocyte.

Background Tumor-treating fields (TTFs) have become an important, evidence-based modality in the treatment of glioblastoma (GBM). In patients requiring cardiac pacemakers, TTF therapy is complicated by theoretical concerns regarding possible electrical interaction between the devices. Case Description A 57-year-old man with past medical history of sick sinus syndrome requiring cardiac pacemaker implantation suffered an acute neurologic change associated with a left parieto-occipital lesion, which was found to be GBM. After completion of guideline-concordant chemoradiation, he chose to undergo TTF therapy. Because of the absence of cardiac symptoms and the theoretical risk of far-field sensing by the pacemaker of the TTF device (potentially resulting in pacemaker inhibition), the pacemaker was turned off before receiving TTF. Following TTF implementation, the patient responded well; he remains alive more than 25 months following his GBM diagnosis, exceeding the median 20.9-month survival of the recently completed phase III TTF randomized clinical trial for newly diagnosed GBM. Furthermore, he has exhibited neither cardiac morbidity nor adverse scalp reactions to TTF therapy. Conclusions The first reported case of successful TTF administration in a GBM patient with a previously implanted cardiac pacemaker may allay the concerns of neuro-oncologists, cardiologists, radiation oncologists, and all certified TTF prescribers regarding the applicability of TTF in suitable candidates with preexisting cardiac pacemakers. This case indicates that TTF therapy may be efficacious in patients with indwelling magnetic resonance image−conditional cardiac pacemakers turned to the off position and that physical removal of the pacemaker is not necessary before starting TTF.

Electrical coupling between cardiomyocytes is important in synchronous beating and normal heart functions. Cardiomyocytes are also electrically coupled to non-cardiomyocytes. The electrical interactions between cardiomyocytes and non-cardiomyocytes, or those between separated cardiomyocytes, are important for normal heart function because abnormalities of the coupling and variation of the cell population induce pathological heart functions and arrhythmias. In this study the three-dimensional time course of the electrical interaction between two rat neonatal cardiomyocyte sheets separated by non-cardiomyocyte sheets was analysed by a multiple-electrode extracellular recording system. The two cardiomyocyte sheets separated by a single- or double-layered mouse fibroblast NIH3T3 cell sheet coupled electrically at 113 ± 28 or 287 ± 87 min after layering, respectively. The time course of the electrical coupling, when the single-layer NIH3T3 cell sheet was inserted, is similar to that of a layered cardiomyocyte sheet. Immunocytological analysis and dye transfer assay suggested the formation of gap junctions at heterocellular junctions of cardiomyocytes and NIH3T3 cells. On the other hand, when a double-layered NIH3T3 cell sheet was inserted, an incomplete electrical coupling of two cardiomyocyte sheets, including a conduction delay, was observed. The electrical coupling of cardiomyocyte sheets was completely blocked (conduction block) by insertion of a triple-layered NIH3T3 cell sheet, a communication-defective HeLa cell sheet or a Ca2+-antagonist LaCl3-treated cell sheet. These electrophysiological analyses of heterogeneously stacked cell sheets might provide insights into complex electrical conduction systems that resemble those of native or damaged heart and transplanted tissues. Copyright © 2009 John Wiley & Sons, Ltd.

cited By 18; International audience; Carbon multi-walled nanotubes (MWCNTs) may have several dangerous effects on different cell systems, but the mechanisms responsible for their cytotoxicity are not well known yet. At present, very little is known about the electrical interactions between nanomaterials and cells. We aimed to verify whether MWCNT electrical properties could affect the so called "charge-sensitive" cell parameters, interacting with cellular electrical activity. Human macrophages were challenged with two fully characterised MWCNT samples, one tested as-prepared (MWCNT), the other one purified (by annealing at 2400 °C) and better electro-conductive (a-MWCNT). Our findings show that a-MWCNTs are less cytotoxic but possess a higher inflammatory potential, as compared to MWCNTs. Moreover, only annealed and better conductive MWCNTs affect significantly the mitochondrial membrane polarity, the intracellular pH and the reorganisation of cytoskeleton actin filaments, cell functions strictly dependent on electro-chemical mechanisms. Based on our results, there is evidence for electro-chemical interactions taking place between cell membranes and electro-conductive MWCNTs. Such a specific behaviour could have wide-range applications in the biomedical field, not only concerning those cellular systems (neuronal and bone cells) sensitive to electrical stimuli, but also other cell systems.

Background— The growing population with Fontan operation surviving into adulthood has significant morbidity and mortality rates from recurrent atrial tachyarrhythmias. We hypothesized that the structural characteristics and electrical behavior of atria may differ in these patients compared with those without arrhythmias. Methods and Results— We studied 33 consecutive patients (age, 25.4±9.5 years) with Fontan circulation, of whom 19 had a history of documented sustained atrial tachyarrhythmias. We analyzed their clinical and investigational data, including echocardiographic assessment of atrial dimensions and surface 12-lead ECG measurement of the P-wave duration and its dispersion between leads. Twenty age- and sex-matched healthy control subjects were also studied. First, patients who had the Fontan procedure overall had longer P-wave duration (144±33 versus 100±7 ms, P P P P P =0.01). Third, both P-wave duration and dispersion were significantly correlated to right atrial dimension within the Fontan group ( r =0.55, P =0.002, and r =0.56, P =0.002, respectively). Conclusions— Patients with atrial tachyarrhythmias late after Fontan operation have longer P-wave duration and P-wave dispersion and larger right atrial dimension than those without the arrhythmias; these abnormalities are interrelated. This observation represents an atrial mechano-electrical remodeling phenomenon in parallel to an increase in arrhythmia propensity in this vulnerable population and warrants further investigation.

The role of electrical interaction in wound healing has been recognized for nearly half of the last century. Based on the notion that wound healing may be facilitated by using electrical stimulation (referred to as electrotherapy), numerous animal model studies and clinical trials have been carried out to establish the effectiveness of electrotherapy. In spite of the concentrated effort, however, electrotherapy has not been approved by the U.S. FDA and remains poorly understood. Elucidation of the molecular and cellular mechanisms mediating facilitated wound healing is likely required, before rational electrotherapy can be devised and successfully implemented. Over the past six years, we have performed a series of in vitro experiments designed to identify the mechanisms mediating the cellular effects induced by exogenous application of electrical stimulation. The purpose of this review is to provide a description for such mechanisms (i.e., electrocoupling mechanisms) and to formulate an integrated model for these coupling mechanisms.

Cochlear implants are devices which are surgically inserted into the internal ear, partially restoring hearing to people with profound deafness. Alternatives to improve levels of auditory perception are to increase the number of channels or frequency bands, that would need to increase the number of electrodes or electrode pairs per channel. Monopolar Virtual Channel (MPVC) stimulation mode increases the number of channels without increasing the number of electrodes using current steering. With this stimulation mode what still happens is interaction between the virtual channels, so some people who have these implants have not reported a striking improvement. In the present work, parameters of this electrical stimulation mode are modeled and evaluated. The results suggested that the maximal stimulation current can be determine so that no electrical interaction will occur between adjacent channels. If the stimulation current is higher than the calculated value, electrical interactions will occur between adjacent channels.

Conclusions: Phased-array stimulation is a promising technique, which uses electrical interaction to focus the stimulation in cochlear implants, at the expense of limited threshold shifts. It has potential advantages over, for example, tripolar stimulation. Objectives: Current spread imposes limitations in cochlear implants. Van Compernolle (1985) suggested using all electrode contacts simultaneously to reduce these effects. Van den Honert et al. (2007) validated this so-called phased array algorithm in patients with respect to the electrode potentials but the effect on neural excitation remained unclear. The present study used computational modeling to relate the effect of phased-array stimulation to the neural elements. Methods: A computational model of the implanted human cochlea was used to compare the neural excitation patterns induced by conventional monopolar stimulation and by phased-array stimulation. Neural thresholds and electrical dynamic ranges were visualized with excitation profiles, showing the auditory nerve's response to a range of stimulus levels. Results: Phased-array stimulation of a single region reduces the spread of excitation and increases the dynamic range. The phased array paradigm can be extended to stimulate multiple sites simultaneously, thereby eliminating the need for sequential stimulation, but with a more limited range of usable stimulus levels, especially with perimodiolar electrodes.

As Dyer highlights in his article on the Taser conducted energy device,1 one of the unresolved controversies surrounding the effects of the Taser is whether the discharge can influence heart rhythm through a direct electrical interaction. This controversy has been aired recently in the journal Circulation .2 3 In our February 2010 editorial for The BMJ …

Physiological U wave genesis occurs likely secondary to either late repolarisation of Purkinje fibres, or late repolarisation of some myocardial cells and/or delayed after depolarisation of the ventricular wall occurring during ventricular filling. Hypokalaemia has a well-known association with pathological 'U wave' which actually combines with the T wave (TU complex) and results from slowing of phase 3 of the action potential with resultant electrical interaction between the three myocardial layers. U waves usually tend to disappear in the setting of hyperkalaemia. We report an unusual case where hyperkalaemia and discordant U waves coexisted. We believe that this may have occurred as a result of partial clinical adaptation of cardiac myocytes to the long-standing effects of hyperkalaemia as the patient had underlying history of chronic kidney disease. We also discuss the possible mechanisms of the U wave genesis and the importance of different U wave morphologies encountered in the real clinical practice.

1. The electrical threshold of the terminations of single group Ia and II afferent fibers was transiently reduced by the antidromic discharge of the initial segment of spinal motoneurons in the cat. 2. This depolarization of the terminals of afferent fibers known to synapse on motoneurons confirms previous observations of antidromic electrical interaction between these structures.

To investigate electrical interaction among large cells in the lobster cardiac ganglion, electrotonic transmission between the somata of two such cells was observed by applying current pulses of two different durations and recording induced responses in the membrane potential of soma. The brief potential changes induced in one soma were transmitted to an adjacent soma through electrotonic pathways in the same way as the longer potential changes. However attenuation was greater for the shorter pulses. The amplitude of the soma spike markedly decreased compared to that of the axon spike, and the ratio was about 5.5. The soma spike was not a regenerative response of the soma membrane, but it was an electrotonic spread of the axon spike. The attenuation ratio of the soma spike was almost the same as that measured for a brief potential change such as a spike applied to the soma. These findings indicate that the soma spike spreads electrotonically to the adjacent soma through the electrical connections, while the axon spike does not. Such electrical transmission of the spike was extremely weak. The slow potential, electronic transmission of which had been observed between large cells, was restricted to the soma. The results suggest that the electrotonic pathways interconnect the somata of large cells in the anterior part of the ganglionic trunk, but not the axons. Electrical transmission of the spike through the pathways is very weak because of the inexcitable membrane of the somata. The electrotonic pathways are considered to be fibre-like connections between dendrites arising from the somata.

A model of the electrical activity of excitable membrane was used to simulate action potential propagation in cardiac cells. Using an implicit method for solving finite difference equations, propagation through the intercalated disc region between two abutting cells was studied. A model of interaction was constructed and parameters of the cellular junction determined. Estimates of the intercalated disc resistance were then made from these junction parameters using a field analysis of the junction. Values of approximately 4 Omega-cm(2) were found and correlate well with experimentally measured values.

1. Electrical interactions have been studied in the isolated frog spinal cord preparation. It is found that gallamine and tetraethylammonium chloride (TEA) markedly enhance all non-cholinergic synaptic interactions, including the electrical interaction between motoneurones (VR-VRP). In addition, in the presence of either of these drugs, a short-latency interaction is seen to exist between antidromically stimulated motoneurones and dorsal root afferents (early VR-DRP). The early VR-DRP is rarely seen in the absence of gallamine or TEA. 2. The early VR-DRP is of the same short latency as the VR-VRP and fulfils the same criteria for electrical interaction: it increases in amplitude with cooling from 17-10° C, it is not blocked by a wide variety of pharmacological blocking agents, and it is suppressed by both Mg2+ and Ca2+, with no antagonism of action between the two. 3. The early VR-DRP appears as a cluster of unitary events: all-or-none spikes conducted out the dorsal root fibres. No initial graded slow potentials are seen. Often there are two peaks in the response. 4. The early VR-DRP is facilitated by a dorsal root volley, with a time course normally intermediate between that of the orthodromic ventral root potential (DR-VRP) and the dorsal root potential (DR-DRP). This orthodromic facilitation apparently is achieved by increasing invasion of motoneurone dendritic trees and depolarization of dorsal root afferents toward threshold. 5. If the same ventral root is stimulated twice, or adjacent roots stimulated at different intervals, the second early VR-DRP, like the VR-VRP, is seen to be occluded for 10-20 msec, then facilitated to supranormal amplitudes. It is concluded that motoneurone dendrites are presynaptic to both interactions. 6. Evidence is presented that gallamine and TEA act by increasing the duration of activity both in axon terminals and in antidromically invaded motoneurones. Often second or multiple spikes result. The increased duration of depolarization can increase transmitter release at terminals and increase coupling at electrical junctions. 7. Possible morphological correlates for the two electrical interactions are discussed. It is speculated that the motoneurone interaction arises at numerous areas of close apposition between dendrites in dendritic `thickets', and that the early VR-DRP is mediated by fewer, lower-resistance, electrical junctions between dendrites and afferent nerve terminals.

Facilitation and excitation of motoneurons through antidromic impulses in ventral root fibers of an adjacent segment in the spinal cord of Xenopus laevis were investigated. The method of monosynaptic testing was employed. Orthodromically elicited monosynaptic ventral root reflex responses were strongly facilitated by antidromic volleys of impulses in neighboring ventral root fibers. The latency of this facilitatory effect was apparently too short to assume the presence of chemically transmitting synapses in the pathway. Electrical interaction between motoneurons seems to be the more likely explanation. In some preparations motoneurons were excited to the firing level in response to an antidromic stimulus only, when this was applied to neighboring ventral root fibers. This response was greatly facilitated by a preceding conditioning orthodromic volley. The latency of the response to the antidromic stimulus was relatively long and comparable to that of monosynaptic activation. These results might be accounted for by assuming synaptically mediated excitation through recurrent axon collaterals which terminate on neighboring motoneurons. The mechanism of this interaction between neighboring motoneurons therefore remains uncertain.

When two cardiac pacemaker cells of different intrinsic beat frequencies are coupled electrically by nexal junctions, they exchange current through the nexal conductance. This electrical interaction interferes with the original beat rate of both cells, and if the nexal resistance is low enough, it may result in synchrony, i.e. in a simultaneous or almost simultaneous occurrence (with constant phase difference) of action potentials at the same frequency. This frequency may be different from the intrinsic frequency of either cell (DeHaan and Hirakow, 1972; Ypey et al., 1979). Whether synchrony results, depends both on the properties of the nexal and the non-nexal (excitable) membranes of the cells. For example, two coupled pacemaker cells may require a different nexal conductance to obtain synchrony if one of the two cells changes its intrinsic rate (Ypey et al., 1980).

Publisher Summary This chapter discusses the role of the catalytic anionic site in acetylcholinesterase. The active site of acetylcholineeterase interacts with acetylcholine at two subsites, the catalytic anionic site and the esteratic site. The anionic site is characterized by a negative charge and hydrophobic areas and is thought to facilitate catalysis mainly by binding and orienting the substrate. However, the role of the anionic site may not be limited to merely binding and orienting. The binding of acetylcholine to acetylcholineeterase results mainly from the electrical interaction between the anionic site and the quaternary head of the substrate and from the hydrophobic interaction between the anionic site and the methyl groups on acetylcholine. The first interaction contributes around 8 kJ/mol and the second one about 16. It is clear that (a better) binding to the anionic site by itself accelerates hydrolysis only under certain conditions. The acceleration by binding is greater if the binding by the anionic site of the transition state is greater than the binding of the substrate; moreover, in this case the acceleration appears under all conditions.

Interaction between nerve cells mediated by electrical coupling is a common feature of the nervous system (for a review see Bennett, 1977). This interaction may be specific to a restricted number of cells, or even to part of a cell as in the case of the electrical inhibition in the initial segment of the Mauthner fibre (Korn and Faber, 1975).

The term electroanatomy was introduced by von Bekesy (1951) during his studies aimed at determining the resistance and capacitance patterns that corresponded to the structural features of the cochlea. Considerations of gross impedance configurations (studied by several groups in recent years: Kurokawa, 1965; Johnstone et al., 1966: Honrubia and Ward, 1969; Strelioff, 1973; Honrubia et al. 1976; Cannon, 1976; Geisler et al., 1977) may now be refined by incorporating individual hair cell characteristics. Recent intracellular recordings from mammalian hair cells (Russell and Sellick, 1978; Dallos et al., 1982) provide various electrical measures that describe the properties of these cells and highlight differences between inner (IHC) and outer hair cells (OHC). The purpose of this paper is to consider a simple circuit model of a cochlear cross-section and to investigate relationships between computed electrical quantities and those obtained experimentally. It is shown that several hitherto baffling differences between IHC and OHC electrical properties are a simple consequence of their impedance configurations. The results also suggest that electrical interactions between OHCs and IHCs are highly unlikely.

Longitudinally-oriented bundles of closely-aligned motoneuron dendrites in Lamina IX of cat spinal cord were examined. These dendrites were interrelated in one of several ways: (1) They were separated by a space of several microns containing small myelinated and unmyelinated fibers, synaptic boutons, and glial processes; (2) Some dendrites were separated by a gap of 0.2–0.5 μ which contained only an attenuated astrocyte process; (3) The plasma membranes of the adjacent dendrites were occasionally found in direct apposition and in most of these instances there was no detectable specialization of the opposing membranes; (4) There were definite modifications along the appositional membranes. These zones were characterized by a gap of ∼ 180 A, and symmetrical, non-polarized aggregations of electron-opaque material were found along the cytoplasmic surfaces of the membranes. It is suggested that the spatial arrangement and appositional relations of these dendrites represent a morphological substrate for the weak electrical facilitation known to occur between motoneurons in the cat spinal cord.

Various patterns of burst activity in the cardiac ganglion cells of the crab Eriocheir japonicus were observed by means of intracellular electrodes. The pacemaker for burst initiation is located among small cells, and it induces small synaptic potentials in the large cells, increasing their excitability. The anterior large cells generate slow potentials by synaptic activation. The slow potential is the spike generator. The anterior large cells are capable of initiating slow potentials in their own somata without synaptic activation from the small cell. Non-synaptic maintained depolarization takes place in the anterior large cell membrane. The after-depolarizations are cumulative and can develop the slow potential, leading to repetitive firing. The posterior large cell is innervated by two pre-synaptic nerve fibres, one being the small pacemaker cell and the other the anterior large cell, showing that it is a follower. Electrical interaction is present among ganglion cells. Positive feedback through electrical connexions is observed between large and small cells. The cardiac ganglion of the crab has some features common and similar to those found in the ganglia of both the lobster and Squilla.

Summary Neuropile of the amphibian spinal cord was studied by light and electron microscopy to determine whether there are intercellular relations involving dendrites which would provide support for electrical interaction between montoneuron dendrites. Golgi studies show dendrites of monotoneurons to extend for long distances in a rostro-caudal direction, and electron micrographs reveal dendrodendritic contacts to be common in the vicinity of motoneuron somata. However, no membrane specializations were seen, and the percentage of the dendrite surface apposed to other dendrites is quite small except in small, circumscribed areas referred to as dendrodendritic ‘thickets’ where approximately 15% of the surface of large dendrites involves such contacts. Measurements were also made showing appositional relations of axons, astrocytes, and other elements to neuron somata and dendrites.