Membrane Electrical Properties Research Articles

Membrane excitability and excitation–contraction uncoupling in muscle fatigue

High-frequency tetanic stimulation is associated with an increase in extracellular and T-tubular K(+) and changes of Na(+) and Cl(-) concentrations, membrane depolarization as well as inactivation of voltage-gated Na(+) channels. These alterations are expected to lead to fiber inexcitability, which is largely prevented by mechanisms intrinsic or extrinsic to muscle fibers. They act by adapting electrical membrane properties or by accelerating the reconstitution of ionic homeostasis. The high Cl(-) conductance of muscle fibers supports the K(+) conductance in fast and complete repolarization and creates a mechanism for the fast reuptake of K(+), thereby reducing the T-tubular K(+) accumulation. Excitability is increased by a Ca(2+) and proteinkinase C dependent inhibition of the Cl(-) conductance which is efficient especially in the T-tubular system. Several mediators activate the Na(+)/K(+)-ATPase and thus enhance the restoration of ionic homeostasis. Examples are purines (ATP, ADP), calcitonin-gene related peptide and adrenaline. It is also necessary to adapt the strength of the sarcoplasmic Ca(2+) concentration to the requirements of tetanic contractions. An overwhelming Ca(2+) signal leads to enzymatically driven excitation-contraction uncoupling. This process is most likely driven by the Ca(2+) dependent protease μ-calpain and might lead to the long-lasting fatigue observed after excessive physical activity.

Effect of LiBr pore-filling on morphological, optical and electrical properties of porous silicon membrane

This study describes the developmental properties of PS membrane derived from the pore-filling with aqueous LiBr solutions. A complete process is described and the effect of pore-filling with Lithium bromide (LiBr) on PS membrane structural, optical and electrical properties is investigated. The microstructural and surface morphology of the elaborated samples were characterized mainly by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The AFM shows an increase of the nanoparticles dimension compared to the initial dimension of the PS membranes nanostructure. This result shows that LiBr covers the nanoparticles of PS membranes, which was confirmed by photoluminescence study. A modification of PS membranes morphology accompanied with significant decrease of reflectivity. The rise of the conductivity is significant after pore-filling with LiBr solution. The conductivities of porous silicon membrane are 0.021S/cm before pore-filling and 0.019S/cm after pore-filling with LiBr solution. This suggests the choice of LiBr as filler to improve the electrical conductivity of porous silicon membrane.

Adult‐like action potential properties and abundant GABAergic synaptic responses in amygdala neurons from newborn marmosets

The amygdala plays an important role in the processing of emotional events. This information processing is altered by development, but little is known about the development of electrophysiological properties of neurons in the amygdala. We studied the postnatal development of electrophysiological properties of neurons in the basolateral amygdala (BLA) of the common marmoset (Callithrix jacchus). Whole-cell patch-clamp recordings were obtained from BLA pyramidal neurons in brain slices prepared from developing and adult marmosets, and electrophysiological properties known to change during development in rats were analysed. Two passive electrical properties of the neuronal membrane - the input resistance (R(in)) and the membrane time constant () - significantly decreased with postnatal development. In contrast, the action potential only showed a slight decrease in duration during the first month of life, whereas the amplitude did not change after birth. Passive electrical properties and action potentials in neurons of 4-week-old marmosets were similar to those in neurons of 4-year-old marmosets. The development of the action potential duration was not correlated with the development of R(in) or , whereas the development of R(in) and was correlated with each other. Abundant spontaneous and noradrenaline-induced GABAergic currents were present immediately after birth and did not change during postnatal development. These results suggest that newborn infant marmoset BLA pyramidal neurons possess relatively mature action potentials and receive vigorous GABAergic synaptic inputs, and that they acquire adult-like electrophysiological properties by the fourth week of life.

The Trk A, B, C's of Neurotrophins in the Cochlea

The spiral ganglion neurons (SGNs) are the afferent neurons of the cochlea, connecting the auditory sensory cells-hair cells-to the brainstem cochlear nuclei. The neurotrophins neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) are expressed in the cochlea and both support SGN survival during development. These neurotrophins remain expressed in the postnatal cochlea and continue to play additional roles for SGNs, contributing to maintenance of hair cell-SGN synapses and regulating expression of ion channels, presynaptic and postsynaptic proteins, and SGN membrane electrical properties in a physiologically important spatial pattern. Remarkably, NT-3 and BDNF have different, even opposing, effects on SGN physiology despite the close similarity of their receptors TrkB and TrkC. Recent studies have also raised the possibility that precursor proneurotrophin forms of the neurotrophins play a role in responses to trauma in the cochlea, signaling through the proneurotrophin receptor p75(NTR) . Here, we review expression and function of neurotrophins and their p75(NTR) and Trk-family receptors in the cochlea. We focus, in particular, on neurotrophin functions other than support of SGN survival, including regulation of SGN neurite growth, synaptic and membrane physiology. These functions, unlike survival, are ones for which BDNF and NT-3 substantially differ in their effects. Signal transduction mechanisms of p75(NTR) and of Trk-family receptors are discussed, indicating how these lead to different responses, and we speculate on how BDNF and NT-3 can cause different phenotypic changes in SGNs. Because these complex signaling interactions remain incompletely understood, use of neurotrophins as therapeutic agents in the cochlea should be approached with caution.

Electrochemical Impedance Spectroscopy and Atomic Force Microscopic Studies of Electrical and Mechanical Properties of Nano-Black Lipid Membranes and Size Dependence

We present electrochemical impedance spectroscopic (EIS) and two-chamber AFM investigations of the electrical and mechanical properties of solvent-containing nano-BLMs suspended on chip-based nanopores of diameter of 200, 400, and 700 nm. The chips containing nanoporous silicon nitride membranes are fabricated based on low-cost colloidal lithography with low aspect ratio of the nanopores. BLMs of DPhPC lipid molecules are constructed across the nanopores by the painting method. Two equivalent circuits are compared in view of their adequacy in description of the EIS performances of the nano-BLMs and more importantly the structures associated with the nano-BLMs systems. The BLM resistance and capacitance as well as their size and time dependence are studied by EIS. The breakthrough forces, elasticity in terms of apparent spring constant, and lateral tension of the solvent-containing nano-BLMs are investigated by AFM force measurements. The exact relationship of the breakthrough force of the nano-BLM as a function of pore size is revealed. Both EIS and AFM studies show increasing lifetime and mechanical stability of the nano-BLMs with decreasing pore size. Finally, the robust 200 nm diameter nanopores are used to accommodate functional BLMs containing DPhPC lipid molecules and gramicidins by using a painting method with drop of mixture solutions of DPhPC and gramicidins. EIS investigation of the functional nano-BLMs is also performed.

A Compartmental Model of Linear Resonance and Signal Transfer in Dendrites

Dendrites carry signals between synapses and the soma and play a central role in neural computation. Although they contain many nonlinear ion channels, their signal-transfer properties are linear under some experimental conditions. In experiments with continuous-time inputs, a resonant linear two-port model has been shown to provide a near-perfect fit to the dendrite-to-soma input-output relationship. In this study, we focused on this linear aspect of signal transfer using impedance functions that replace biophysical channel models in order to describe the electrical properties of the dendritic membrane. The membrane impedance model of dendrites preserves the accuracy of the two-port model with minimal computational complexity. Using this approach, we demonstrate two membrane impedance profiles of dendrites that reproduced the experimentally observed two-port results. These impedance profiles demonstrate that the two-port results are compatible with different computational schemes. In addition, our model highlights how dendritic resonance can minimize the location-dependent attenuation of signals at the resonant frequency. Thus, in this model, dendrites function as linear-resonant filters that carry signals between nonlinear computational units.

The LIM-Homeodomain Protein Islet Dictates Motor Neuron Electrical Properties by Regulating K+ Channel Expression

SummaryNeuron electrical properties are critical to function and generally subtype specific, as are patterns of axonal and dendritic projections. Specification of motoneuron morphology and axon pathfinding has been studied extensively, implicating the combinatorial action of Lim-homeodomain transcription factors. However, the specification of electrical properties is not understood. Here, we address the key issues of whether the same transcription factors that specify morphology also determine subtype specific electrical properties. We show that Drosophila motoneuron subtypes express different K+ currents and that these are regulated by the conserved Lim-homeodomain transcription factor Islet. Specifically, Islet is sufficient to repress a Shaker-mediated A-type K+ current, most likely due to a direct transcriptional effect. A reduction in Shaker increases the frequency of action potential firing. Our results demonstrate the deterministic role of Islet on the excitability patterns characteristic of motoneuron subtypes.

Steady-state and transient electrical properties of ion-exchange membrane systems in asymmetric arrangements

The steady-state and transient electrical properties of ion-exchange membranes placed between two solutions with different values of the electrolyte concentration, have been simulated using the network simulation method. The ionic transport processes are theoretically described on the basis of the Nernst-Planck and Poisson equations. The system under study is constituted by a cation-exchange membrane in which the fixed-charge is homogeneously distributed in space and two diffusion boundary layers on both sides of the membrane, the electric double layers at the interfaces being included. The steady-state voltage-current characteristic and the profiles of the ionic concentrations and the electric potential, are analysed. Also, the choronopotentiometric response of the system has been discussed and the time evolution of the electric energy consumption evaluated. In particular, the influence of the ratio of the bathing concentrations on the permselectivity and the chronopotentiometric response of the ion-exchange membrane systems, has been established.

Embryonic assembly of auditory circuits: spiral ganglion and brainstem

During early development, peripheral sensory systems generate physiological activity prior to exposure to normal environmental stimuli. This activity is thought to facilitate maturation of these neurons and their connections, perhaps even promoting efficacy or modifying downstream circuitry. In the mammalian auditory system, initial connections form at embryonic ages, but the functional characteristics of these early neural connections have not been assayed. We investigated processes of embryonic auditory development using a whole-head slice preparation that preserved connectivity between peripheral and brainstem stations of the auditory pathway. Transgenic mice expressing fluorescent protein provided observation of spiral ganglion and cochlear nucleus neurons to facilitate targeted electrophysiological recording. Here we demonstrate an apparent peripheral-to-central order for circuit maturation. Spiral ganglion cells acquire action potential-generating capacity at embryonic day 14 (E14), the earliest age tested, and action potential waveforms begin to mature in advance of comparable states for neurons of the ventral cochlear nucleus (VCN) and medial nucleus of the trapezoid body (MNTB). In accordance, auditory nerve synapses in the VCN are functional at E15, prior to VCN connectivity with the MNTB, which occurs at least 1 day later. Spiral ganglion neurons exhibit spontaneous activity at least by E14 and are able to drive third-order auditory brainstem neurons by E17. This activity precedes cochlear-generated wave activity by 4 days and ear canal opening by at least 2 weeks. Together, these findings reveal a previously unknown initial developmental phase for auditory maturation, and further implicate the spiral ganglion as a potential controlling centre in this process.

Irradiation Effect of Gamma Ray on Electrical Characteristics of Perfluorosulfonic Acid Polymer Membrane

Perfluorosulfonic acid polymer membranes, such as Nafion®, Aciplex®, and Flemion®, are attracting great attention as electrolyte membranes for fuel cells because they have high proton conductivity. In this paper, the effect of γ rays on the electrical properties of perfluorosulfonic acid membranes by applying a variable voltage and measuring the current and dimension of the sample have been investigated. In order to understand the irradiation effects on conductivity changes, we have used optical absorption measurement in the wavelength of 190 ∼ 500 nm. The results show that the electrical conductivity has been increased by increasing the absorption dose, and intensity of the absorption bands have increased by increasing the absorption dose. The electrical conductivities of the irradiated membranes at room temperature are enhanced about one order of magnitude higher than the conductivities of an unirradiated membrane. Moreover, an optical absorption measurement shows that the structures of the membranes are modified by γ radiation. Intensity absorption bands associated to fluorocarbon and peroxy radicals and C=O groups increased with increasing the dose. The change in electrical conductivity seems to be related to the high production of peroxy radicals in the irradiated membrane.

Activation of glutamate transport evokes rapid glutamine release from perisynaptic astrocytes

Stimulation of astrocytes by neuronal activity and the subsequent release of neuromodulators is thought to be an important regulator of synaptic communication. In this study we show that astrocytes juxtaposed to the glutamatergic calyx of Held synapse in the rat medial nucleus of the trapezoid body (MNTB) are stimulated by the activation of glutamate transporters and consequently release glutamine on a very rapid timescale. MNTB principal neurones express electrogenic system A glutamine transporters, and were exploited as glutamine sensors in this study. By simultaneous whole-cell voltage clamping astrocytes and neighbouring MNTB neurones in brainstem slices, we show that application of the excitatory amino acid transporter (EAAT) substrate d-aspartate stimulates astrocytes to rapidly release glutamine, which is detected by nearby MNTB neurones. This release is significantly reduced by the toxins L-methionine sulfoximine and fluoroacetate, which reduce glutamine concentrations specifically in glial cells. Similarly, glutamine release was also inhibited by localised inactivation of EAATs in individual astrocytes, using internal DL-threo-β-benzyloxyaspartic acid (TBOA) or dissipating the driving force by modifying the patch-pipette solution. These results demonstrate that astrocytes adjacent to glutamatergic synapses can release glutamine in a temporally precise, controlled manner in response to glial glutamate transporter activation. Since glutamine can be used by neurones as a precursor for glutamate and GABA synthesis, this represents a potential feedback mechanism by which astrocytes can respond to synaptic activation and react in a way that sustains or enhances further communication. This would therefore represent an additional manifestation of the tripartite relationship between synapses and astrocytes.

Synergy between Electrical Coupling and Membrane Properties Promotes Strong Synchronization of Neurons of the Mesencephalic Trigeminal Nucleus

Electrical synapses are known to form networks of extensively coupled neurons in various regions of the mammalian brain. The mesencephalic trigeminal (MesV) nucleus, formed by the somata of primary afferents originating in jaw-closing muscles, constitutes one of the first examples supporting the presence of electrical synapses in the mammalian CNS; however, the properties, functional organization, and developmental emergence of electrical coupling within this structure remain unknown. By combining electrophysiological, tracer coupling, and immunochemical analysis in brain slices of rat and mouse, we found that coupling is mostly restricted to pairs or small clusters of MesV neurons. Electrical transmission is supported by connexin36 (Cx36)-containing gap junctions at somato-somatic contacts where only a small proportion of channels appear to be open (∼0.1%). In marked contrast with most brain structures, coupling among MesV neurons increases with age, such that it is absent during early development and appears at postnatal day 8. Interestingly, the development of coupling parallels the development of intrinsic membrane properties responsible for repetitive firing in these neurons. We found that, acting together, sodium and potassium conductances enhance the transfer of signals with high-frequency content via electrical synapses, leading to strong spiking synchronization of the coupled neurons. Together, our data indicate that coupling in the MesV nucleus is restricted to mostly pairs of somata between which electrical transmission is supported by a surprisingly small fraction of the channels estimated to be present, and that coupling synergically interacts with specific membrane conductances to promote synchronization of these neurons.

Effect of membrane properties on skeletal muscle fiber excitability: a sensitivity analysis

In this study, the sensitivity of skeletal muscle fiber excitability to changes in temperature and a range of geometrical, electrical and ionic membrane properties was examined using model simulation. A mathematical model of the propagating muscle fiber action potential (AP) was used to simulate muscle fiber APs while changing individual muscle fiber parameters in isolation to examine how they affect muscle fiber AP amplitude, shape and conduction velocity (CV). The behavior of the model was verified by comparison with previously reported experimental data from both in vivo studies conducted at physiological temperatures and in vitro and in silico studies conducted at lower temperatures. The simulation results presented demonstrate the sensitivity of AP amplitude, shape and CV and, therefore, muscle fiber excitability to small changes in a wide range of different muscle fiber parameters. Furthermore, they demonstrate the potential of computational modeling as a tool for investigating the underlying mechanisms of complex phenomena such as those which govern skeletal muscle excitation.

Escherichia Coli Regulates Cell Division by Modulating Membrane Potential

Indole is a very important biological molecule being produced by more than 85 Gram positive and Gram negative bacterial species, including Escherichia coli. Among its several physiological functions indole is shown to stop bacterial cell division when secreted in large quantities.Here we study the effect of indole on the electrical properties of the lipid membranes. Using electrophysiology, we show that the indole molecules are able to short-circuit lipid membranes. We also show that the rate of mitochondrial oxygen consumption measured in the presence of succinate increases when the indole concentration is titrated up. Therefore indole is capable of lowering the energetic barrier for ion permeation across lipid membranes. Since the bacterial cell division is strongly influenced by the ability of the cell to maintain a membrane potential(1) this is the first example of a bacterium using an ionophore to regulate the bacterial cell division. These findings have implications for our understanding of membrane biology, bacterial cell cycle control and potentially for the design of antibiotics that target the cell membrane.1. Strahl, H. & Hamoen, L.W. Membrane potential is important for bacterial cell division. Proceedings of the National Academy of Sciences 107, 12281-12286 (2010).

Conductive AFM: Probing Nano-scale Electrical Properties of Model Cell Membranes

ABSTRACTBiologically relevant lipid bilayers supported on highly ordered pyrolytic graphite (HOPG) were probed both mechanically and electrically with a Conductive Atomic Force Microscope (C-AFM) capable of measuring ultra-low currents. Results show that these membranes undergo an elastic response up to 26 nN on average when compressed with an AFM tip. Measuring the films with a low contact force demonstrates that contact mode AFM can be used repeatedly to image without damaging the film. Based on current-voltage measurements made with the C-AFM, it is shown that apparently high resistances seen for the films could be the result of variable electrical contact between the tip and surface. As a result, the paper proposes that the deflection of the cantilever should always be measured in order to ensure knowledge of the location of the tip during all electrical measurements.

Long-Lasting Alterations in Membrane Properties, K+ Currents, and Glutamatergic Synaptic Currents of Nucleus Accumbens Medium Spiny Neurons in a Rat Model of Alcohol Dependence

Chronic alcohol exposure causes marked changes in reinforcement mechanisms and motivational state that are thought to contribute to the development of cravings and relapse during protracted withdrawal. The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system. Although the NAcc plays an important role in mediating alcohol-seeking behaviors, little is known about the molecular mechanisms underlying alcohol-induced neuroadaptive changes in NAcc function. The aim of this study was to investigate the effects of chronic intermittent ethanol (CIE) treatment, a rat model of alcohol withdrawal and dependence, on intrinsic electrical membrane properties and glutamatergic synaptic transmission of medium spiny neurons (MSNs) in the NAcc core during protracted withdrawal. We show that CIE treatment followed by prolonged withdrawal increased the inward rectification of MSNs observed at hyperpolarized potentials. In addition, MSNs from CIE-treated animals displayed a lower input resistance, faster action potentials (APs), and larger fast afterhyperpolarizations (fAHPs) than MSNs from vehicle-treated animals, all suggestive of increases in K+-channel conductances. Significant increases in the Cs+-sensitive inwardly rectifying K+-current accounted for the increased input resistance, while increases in the A-type K+-current accounted for the faster APs and increased fAHPs in MSNs from CIE rats. We also show that the amplitude and the conductance of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated mEPSCs were enhanced in CIE-treated animals due to an increase in a small fraction of functional postsynaptic GluA2-lacking AMPARs. These long-lasting modifications of excitability and excitatory synaptic receptor function of MSNs in the NAcc core could play a critical role in the neuroadaptive changes underlying alcohol withdrawal and dependence.

Altered Voltage Dependent Calcium Currents in a Neuronal Cell Line Derived From the Cerebral Cortex of a Trisomy 16 Fetal Mouse, an Animal Model of Down Syndrome

Human Down syndrome (DS) is determined by the trisomy of autosome 21 and is expressed by multiple abnormalities, being mental retardation the most striking feature. The condition results in altered electrical membrane properties (EMPs) of fetal neurons, which are qualitatively identical to those of trisomy 16 fetal mice (Ts16), an animal model of the human condition. Ts16 hippocampal cultured neurons reportedly exhibit increased voltage-dependent calcium currents (I (Ca)) amplitude. Since Ts16 animals are unviable, we have established immortalized cell lines from the cerebral cortex of Ts16 (named CTb) and normal littermates (named CNh). Using the whole-cell patch-clamp technique, we have now studied I (Ca) in CTb and CNh cells. Current activation occurs at -40mV in both cell lines (V (holding)=-80mV). Trisomic cells exhibited a 2.4 fold increase in the maximal Ca(2+) current density compared to normal cells (CNh=-6.3±0.77 pA/pF, n=18; CTb=-16.4±2.423 pA/pF; P<0.01, n=13). Time dependent kinetics for activation and inactivation did not differ between the two cell types. However, steady state inactivation studies revealed a 15mV shift toward more depolarized potentials in the trisomic condition, suggesting that altered voltage dependence of inactivation may underlie the increased current density. Further, the total charge movement across the membrane is increased in CTb cells, in agreement with that expected by the potential sensitivity shift. These results indicate that CTb cells present altered Ca(2+) currents, similar to those of Ts16 primary cultured central neurons. The CTb cell line represents a model for studying DS-related impairments of EMPs.

Abstract 16943: Dissecting the Molecular Interaction of Caveolin3 and the Regulatory Subunit (SUR2) of Cardiac KATP Channels

Macromolecular signaling complexes including ion channels present in caveolar microdomains can provide highly specific and localized regulation of cell function. Prior studies have shown that Caveolin3 (Cav3) may interact with a Kir6.2 pore of the cardiac ATP-sensitive potassium channels (KATP). In this report, we studied the molecular interaction of Cav3 and SUR2, the regulatory subunit of KATP. Cav3 and SUR2 were detected in the same caveolar fractions isolated from mouse left ventricles. A P104L-Cav3 mutation was used to probe Cav3-SUR2 trafficking and molecular interaction in COS1 cells. Immunostaining data showed that SUR2 co-localized with Cav3, however, P104L caused retention of SUR2-specific fluorescent signals intracellularly. A quantitative Bioluminescence Resonance Energy Transfer (BRET) assay using coelenterazine-h as substrate was established to study Cav3-SUR2 interaction. WT or P104L-Cav3 was fused to a Renilla Luciferase (Rluc) while SUR2 was fused to YFP. Both WTCav3/SUR2 (0.19±0.04, n=10) and P104LCav3/SUR2 (0.17±0.02, n=10, P=0.05) pairs displayed positive BRET ratios, suggesting that the two proteins were within a 10-100 Å distance to permit energy transfer from RLuc (470-nm) to YFP (530-nm). We did not record positive BRET ratios from negative control samples containing no substrate. Our data showed that Cav3 could directly bind to SUR2, and this interaction was not significantly affected by the P104L mutation, indicating that aa104 is probably not a binding site for the two proteins. To determine which portion of SUR2 binds to Cav3, 3 expression clones harboring SUR2 transmembrane domain TMD0, TMD1 or TMD2 were made. BRET results showed that Cav3 preferably binds to TMD0 (0.19±0.01, n=5) or TMD1 (0.15±0.03, n=5) over TMD2 (0.02±0.01, n=5). Co-immunoprecipitation results confirmed our BRET data. Mouse neonatal myocytes infected with adenoviral particles expressing P104LCav3 displayed a significantly prolonged action potential (APD90, 20.5±4, n=6) than WTCav3-expressing cells (9.3±4, n=4, p&lt;0.05), which suggested that Cav3 levels affected membrane electrical properties. Together with other data, a Cav3-SUR2-Kir6.2 complex that resides in the caveolar microdomains may play an important role in cardiac signaling.

Living systems and liquid crystals

The chemical, physical and electrical properties of naturally occurring liquid crystals are fundamentally linked to the functions of certain biological systems. This review focuses primarily on the liquid crystalline properties of cell membranes and the two-dimensional smectic A model used to describe the lipid bilayer structure that it forms. The composition of mammalian cells is considered along with the effects that disease has on the changes to the molecular composition, and the elastic and electrical properties of the cell membrane. Particular emphasis is given to the role that the flexoelectric effect in a two-dimensional lipid bilayer plays in mechanotransduction (the conversion of a mechanical stimulus to an electrical signal) in living systems. The intrinsic electrical properties arising from the membrane composition itself in terms of the transmembrane, surface and membrane dipole potential are considered in relation to the liquid crystalline structure of the cell membrane and the latest measurement techniques for the measurement of membrane electrical potentials are presented.

The impact of the glial spatial buffering on the K+ Nernst potential

Astrocytes play a critical role in CNS metabolism, regulation of volume and ion homeostasis of the interstitial space. Of special relevance is their clearance of K(+) that is released by active neurons into the extracellular space. Mathematical analysis of a modified Nernst equation for the electrochemical equilibrium of neuronal plasma membranes, suggests that K(+) uptake by glial cells is not only relevant during neuronal activity but also has a non-neglectable impact on the basic electrical membrane properties, specifically the resting membrane potential, of neurons and might be clinically valuable as a factor in the genetics and epigenetics of the epilepsy and tuberous sclerosis complex.