The role of low sodium ion concentrations in the generation of action potentials by neurons of the apple snail (Helix pomatia)

We conducted a comparative investigation of the restorative action of different sodium ion concentrations on generation of action potentials by apple snail neurons of the central nervous system kept for a prolonged period in a solution in which such ions were lacking. Of the 180 neurons investigated, 60% of the cells had lost all excitability, while 40% retained the ability to generate action potentials of normal amplitude. In neurons that ceased under these conditions to generate action potentials both independently and as the result of direct stimulation, amplitude of the action potentials and of the "overshoot" was restored after adding only 2.5–10 mM of sodium to the solution. Analogous concentrations of lithium ions did not exert a similar restorative action. They repressed the capacity of a neuron to regain excitability in the presence of small amounts of sodium ions. Increasing the external concentration of sodium after restoration of the action potentials led to a proportional decline of their amplitude. Keeping neurons in a sodium-containing solution for periods of 25 min and more caused restoration of the neuron's ability to increase linearly the amplitude of action potentials upon raising the external concentration of sodium ions.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 3, pp. 315–322, November–December, 1969.     

Changes in "calcium" action potentials in neurons of the rat spinal ganglia during replacement of divalent cations in the extracellular medium

Single neurons of rat spinal ganglia were investigated in adult rats using a voltage clamping technique and intracellular microelectrodes. Removing sodium ions from the extracellular medium and adding tetraethylammonium to it enabled the calcium component of action potentials to be recorded. It was found that progressive selective suppression of this component takes place during extracellular recording, indicating a decrease in calcium conductivity, while sodium and potassium levels are maintained. It is suggested that this disturbance is caused by excessive influx of calcium, strontium, or barium ions into the cell. The calcium component of action potentials was also found to depend on stimulation rate; this dependence differed where calcium ions were replaced by strontium or barium ions. A possible connection between this effect and the process of voltage-dependent inactivation of calcium channels is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 2, pp. 202–207, March–April, 1986.     

Action of calcium ions on channels of inward and outward currents in the molluscan neuron membrane

Changes in the characteristics of activity of sodium, calcium, and potassium channels in the surface membrane during variation of the calcium ion concentration in the extracellular and intracellular medium were investigated by the voltage clamp method during intracellular dialysis of isolated neurons of the mollusksLimnea stagnalis andHelix pomatia. Besides their direct role in passage of the current through the membrane, calcium ions were shown to have two actions, differing in their mechanism, on the functional properties of this membrane. The first was caused by the electrostatic action of calcium ions on the outer surface of the membrane and was manifested as a shift of the potential-dependent characteristics of the ion transport channels along the potential axis; the second is determined by closer interaction of calcium ions with the specific structures of the channels. During the action of calcium-chelating agents EGTA and EDTA on the inner side of the membrane the conductivity of the potassium channels is substantially reduced. With an increase in the intracellular free calcium concentration the conductivity is partially restored. The action of EGTA and EDTA on the outer side of the membrane causes a substantial decrease in the ion selectivity of the calcium channels and changes the kinetics of the portal mechanism. These changes are easily abolished by rinsing off the chelating agents or by returning calcium ions to the external medium. A specific blocking action of an increase in the intracellular free calcium concentration on conductivity of the calcium channels was found.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 9, No. 1, pp. 69–77, January–February, 1977.     

Development of electrical excitability in embryonic neurons: Mechanisms and roles

Xenopus spinal neurons serve as a nearly ideal population of excitable cells for study of developmental regulation of electrical excitability. On the one hand, the firing properties of these neurons can be directly examined at early stages of differentiation and membrane excitability changes as neurons mature. Underlying changes in voltage-dependent ion channels have been characterized and the mechanisms that bring about these changes are being defined. On the other hand, these neurons have been shown to be spontaneously active at stages when action potentials provide significant calcium entry. Calcium entry provokes further elevation of intracellular calcium via release from intracellular stores. The resultant transient elevations of intracellular calcium encode differentiation in their frequency. Recent studies have shown that different neuronal subpopulations enlist distinct mechanisms for regulation of excitability and recruit specific programs of differentiation by particular patterns of activity. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 190–197, 1998     

Effect of the alkaloid lappaconitine on ionic currents through the somatic membrane ofHelix pomatia neurons

The effect of the alkaloid lappaconitine on passive ion transport through the somatic membrane of identified neurons of the snailHelix pomatia was studied under voltage clamp conditions. In a concentration of 4 mM lappaconitine has a reversible blocking action on the calcium channels of the excitable membrane. To study the effect of the alkaloid on inward sodium currents a solution in which calcium ions were replaced by the equivalent number of magnesium ions was used. Lappaconitine has no appreciable effect on the inward sodium current.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Institute of Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Neirofiziologiya, Vol. 11, No. 5, pp. 469–474, September–October, 1979.     

Involvement of intracellular calcium in sensitization of command neurons of defensive behavior in the edible snail (Helix lucorum)

Examinations carried out on command neurons of defensive behavior in the edible snail using electrophysiological methods and a chlortetracycline fluorescent probe revealed that a single sensitizing action alters electrical neuronal activity and the amount of bound calcium in the cells. An initial increase in the amount of bound calcium (the first 15–20 min after the sensitizing action) coincides in time with depolarization, enhancement of plasma membrane excitability, and a decrease of amplitude and duration of the excitatory postsynaptic potentials (EPSP) induced by sensory stimulations. Repeated pronounced increase in the bound calcium level develops 50–60 min after the sensitizing action and correlates with facilitation of neuronal responses to sensory stimuli. Alterations in the bound calcium level in command neurons of defensive behavior in the course of sensitization development differed in dynamics and direction from the previously described bound calcium shifts in the same cells in the course of habituation development.P. K. Anokhin Institute of Normal Physiology, Academy of Medical Sciences of the USSR Moscow. I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR Leningrad. Translated from Neirofiziologiya, Vol. 23, No. 4, pp. 418–427, July–August, 1991.     

Presumed mechanisms of a long-term increase in the intrinsic excitability of cerebellar granule cells: A model study

Persistent use-dependent changes in the intrinsic neuronal excitability determine the long-term dynamics of the activity of these neurons. In synergy with the long-lasting modification of synaptic transmission, such changes in the excitability presumably contribute to the formation of a memory trace in the brain. Nevertheless, neither particular transmembrane ion conductances implicated in the intrinsic plasticity nor the mechanisms of regulation of such conductances have been identified in most neurons where this plasticity was observed. In our model study, we tried to determine those membrane conductances in cerebellar granule cells (GrCs) whose changes can result in a persistent increase in the input resistance and a decrease in the spike threshold observed after high-frequency stimulation of presynaptic neurons. For this purpose, published experimental results were simulated with the use of a slightly modified model of the electroresponsiveness of rat cerebellar GrCs. It was concluded that experimentally observed changes in the input resistance of the neuron, in the minimum current step needed to fire action potentials (APs), in the spike threshold, in the average spike frequency, and in the delay of the first spike may be caused only by changes in the background voltage-independent potassium conductance and persistent sodium conductance. Hyperpolarization-directed shifts in the activation and inactivation curves of fast sodium channels are also possible. The observed changes in the intrinsic excitability evoke the shift in the peak of the frequency-response curve in such a manner that it becomes close to the frequency of oscillations recorded in the cerebellar granular layer during realization of voluntary movements. Neirofiziologiya/Neurophysiology, Vol. 38, No. 2, pp. 119–130, March–April, 2006.     

Ionic mechanisms of the fast (nicotinic) phase of the acetylcholine response of identified Planorbarius corneus neurons

Responses to electrophoretic application of acetylcholine and suberyldicholine were investigated in identified neurons (LPed-2 and LPed-3) isolated from the left pedal ganglion ofPlanorbarius corneus. When microelectrodes filled with potassium chloride were used the reversal potentials of responses to acetylcholine and suberyldicholine were less negative than when microelectrodes filled with potassium sulfate were used; these reversal potentials were shifted toward depolarization if chloride ions in the medium were replaced by sulfate. These facts indicate that the responses in both LPed-2 and LPed-3 depend on chloride ions. Reversal potentials for acetylcholine and suberyldicholine in LPed-3 were virtually identical (–51 and –50 mV respectively), but in LPed-2 they differed significantly (–46 and –62 mV respectively). Replacement of sodium ions by Tris ions shifted the reversal potential for acetylcholine in LPed-2 toward hyperpolarization but did not change the reversal potential for suberyldicholine. Benzohexonium had the same action. The reversal potential for acetylcholine in medium with a reduced sodium concentration or in the presence of benzohexonium was the same as for suberyldicholine. It is concluded that on neuron LPed-2 acetylcholine activates both acetylcholine receptors which control conductance for chloride ions and acetylcholine receptors which change conductance for sodium ions, whereas suberyldicholine acts only on acetylcholine receptors responsible for the chloride conductance of the membrane.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 12, No. 5, pp. 533–540, September–October, 1980.     

Subtypes of dorsal root ganglion neurons based on different inward currents as measured by whole-cell voltage clamp

Summary Electrophysiological and pharmacological properties distinguished subtypes of adult mammalian dorsal root ganglion neurons (DRGn) in monolayer dissociated cell culture. By analogy of action potential waveform and duration, neurons with short duration (SDn) and long duration (LDn) action potentials resembled functionally distinct subtypes of DRGn in intact ganglia. Patch clamp and conventional intracellular recording techniques were combined here to elucidate differences in the ionic basis of excitability of subtypes of DRGn in vitro. Both SDn and LDn were quiescent at the resting potential. Action potentials of SDn were brief (< 2 msec), sensitive to tetrodotoxin (TTX, 5–10 nM), exhibited damped firing during long depolarizations, and did not respond to algesic agents applied by pressure ejection. Action potentials of LDn were 2–6 msec in duration, persisted in 30 µM TTX, and fired repetitively during depolarizing current pulses or exposure to algesic agents (e.g., capsaicin, histamine and bradykinin). Whole-cell recordings from freshly dissociated neurons revealed two inward sodium currents (I_Na; variable with changes in sodium but not calcium concentration in the superfusate) in various proportions: a rapidly activating and inactivating, TTX-sensitive current; and, a slower, TTX (30 M)-resistant I_Na. Large neurons, presumable SDn, had predominantly TTX-sensitive current and little TTX-resistant current. The predominent inward current of small neurons, presumably LDn, was TTX-resistant with a smaller TTX-sensitive component. By analogy to findings from intact ganglia, these results suggest that fundamentally different ionic currents controlling excitability of subtypes of DRGn in vitro may contribute to functional differences between subtyes of neurons in situ.     

Effects of mibefradil on synaptic transmission in the hippocampus and on voltage-dependent currents in isolated hippocampal and thalamic neurons of the rat

The effects of a novel anti-hypertensive drug, mibefradil, on voltage-dependent currents in isolated thalamic and hippocampal neurons, as well as on synaptic transmission in the hippocampus have been studied. Mibefradil exerted a potent inhibitory action on low-threshold calcium currents in thalamic neurons (IC₅₀=160 nM). In higher concentrations (1–20 μM), this drug blocked not only low-threshold calcium current but also voltage-dependent sodium and delayed potassium currents in pyramidal hippocampal neurons. The amplitude of population action potentials in hippocampal slices decreased by 55% in the presence of 20μM mibefradil. All of the effects of mibefradil were almost completely reversible. In our experiments, the sensitivity of low-threshold calcium channels in thalamic neurons to mibefradil was higher than that observed on other objects. The ability of mibefradil to block not only calcium currents but also other types of voltage-dependent ion conductances in hippocampal neurons may be considered an essential factor that determines the specificity of the pharmacological profile of this drug.     

Action of calcium on the somatic membrane of mollusk giant neurons

Early membrane currents of the isolated neuron soma of the mollusksHelix pomatia,Limnaea stagnalis, andPlanorbis corneus in normal and sodium-free solutions differing in their calcium ion concentration were investigated by the voltage clamp method. The early inward current was shown to continue when the sodium ions in the external solution were replaced by an equivalent number of calcium ions and to be increased with an increase in the concentration of those ions in all neurons of these mollusks investigated. A change in the calcium concentration in the external solution shifted the inactivation curves and also the curves of conductance for the inward current along the potential axis. It is concluded that a system of calcium channels exists in the somatic membrane of neurons in these species of mollusks.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 5, No. 6, pp. 621–627, November–December, 1973.     

Voltage-gated ion channels of inflowing current expressed in Xenopus oocytes after injection of rat brain mRNA

The expression of two types of voltage-gated ion channels of the inflowing current ("fast" sodium channels, sensitive to tetrodotoxin, and high-threshold calcium channels) was detected by electrophysiological methods in the membrane ofXenopus oocytes, after injection of poly(A)⁺-mRNA from the brains of 18- to 20-day-old rats. When Cd²⁺ (200 µmoles/liter) was added to the extracellular solution, the barium current through the expressed calcium channels was completely suppressed, but no sensitivity to D-600 (20 µmoles/liter) and nitrendipine (50 µmoles/liter) was exhibited. A peptide blocker of the high-threshold calcium channels of the neuron membrane, -conotoxin GVIA, in a concentration of 1 µmole/liter led to 20–40 min suppression of the barium current expressed in the oocyte. Steady-state inactivation of this current could be described by the Boltzman formula, using the values of the half-inactivation potential V_1/2=–50 mV and the steepness factor k=14 mV. It is concluded that in potential-dependent and pharmacological properties, the calcium channels expressed in the oocyte, despite the absence of any appreciable time-dependent inactivation, most resemble the high-threshold inactivatable (HTI- or N-type) calcium channels of the neuron membrane.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 3, pp. 344–353, May–June, 1991.     

Influence of medium ionic composition on the electrophysiological properties of the intracardiac-neuron membrane

Replacement of the sodium and chloride ions in the solution bathing a frog heart with an osmotically equivalent sucrose solution leads to hyperpolarization of the neuronal membranes of the intracardiac ganglia and to an increase in their total resistance. The intracardiac neurons continue to respond to stimulation in this solution for some time, producing action-potential spikes, but the amplitude of the potentials is greatly reduced. The neurons also continued to generate action potentials in solutions where the sodium ions were replaced by an osmotically equivalent amount of calcium ions. The amplitude of the potentials increased at first, but action-potential generation was completely inhibited after 14–17 min. The presence of sodium ions in the solution bathing the heart is therefore responsible for development of action potentials in the neurons of the frog intracardiac ganglia.     

Visceral muscles and myogenic activity in the hindgut of the cockroach,Leucophaea maderae

Summary The hindgut of the Madeira cockroach contains an intricate network of longitudinal and circular muscles that are distinctive for each region. In the rectum, the longitudinal muscles are symmetrically arranged in 6 distinct bands, while the circular muscles appear as a uniform layer over the rectal pads. In the colon, the muscle fibers are arranged in an irregular lattice with the longitudinal fibers generally superimposed on the circular ones but with an evident weaving between the layers. In addition to these muscle layers, a delicate, superficial network of muscle-like fibers covers many portions of the colon and rectum.In spite of the bewilderingly complex motile activity of deganglionated hindguts, all activity could be classified under 4 basic types after cinematographic analysis: segmentation, compression, peristalsis, or reverse peristalsis or a combination thereof. Although much of the activity that occurred was seemingly random, there was an evident rhythmicity that spontaneously arose and ended in several types of motility during the course of observations. The defined modes of activity seemed to be completely myogenic in nature, as all 4 categories were readily observed in hindguts 30 min after treatment with tetrodotoxin (10^–6 g/ml). Each region of the hindgut seemed to have its own particular rhythm.Action potentials were recorded both intracellularly and extracellularly from all regions of the hindgut; amplitude usually ranged between 10 and 20 mV for intracellular recordings, and such spike potentials were often preceded by a slow depolarizing pre-potential. Generally, however, the depolarization was abrupt. Transmembrane potentials from the visceral muscle fibers were never truly at rest. Slow, continuous fluctuations (3–8 mV) were common. At times, plateau-type action potentials were recorded, but generally the repolarization contour was almost linear with time. Contractions were evoked by action potentials but not by the slow, rhythmic fluctuations in the membrane potential.No particular region or structure in the hindgut showed an exclusive pacemaker function. However, there was an evident gradient of increased excitability progressing in an caudal direction from the ileum.In a sodium-free saline, the amplitude of action potentials was remarkable enhanced from 5 to 10 min after the initial change. Even after a 20 min exposure, action potentials were still often present although their frequency and amplitude dropped. Tetrodotoxin (10^–6g/ml) had no. pronounced effect on frequency or amplitude of action potentials. However, spike potentials ceased within 1.5 min after exposure to a sodium and calcium-free saline. When such preparations were re-exposed to a sodium-free saline containing normal calcium, the action potentials reappeared, suggesting that calcium might be a current-carrying ion. Although action potentials in a calcium-free medium showed variability, we generally saw a marked reduction in amplitude of potentials within 5 min. We further observed that 2 mM manganous ion completely abolished action potentials within 2 min. Thus, it seems likely that sodium is not the sole current-carrying ion in cockroach hindgut muscle.The authors express their indebtedness to Ms. Susan Swann, Mr. Gerald Holt, Mr. David Owens, and Ms. Mary Strand for their competent technical assistance.     

Morphine Decreases Enteric Neuron Excitability via Inhibition of Sodium Channels

Gastrointestinal peristalsis is significantly dependent on the enteric nervous system. Constipation due to reduced peristalsis is a major side-effect of morphine, which limits the chronic usefulness of this excellent pain reliever in man. The ionic basis for the inhibition of enteric neuron excitability by morphine is not well characterized as previous studies have mainly utilized microelectrode recordings from whole mount myenteric plexus preparations in guinea pigs. Here we have developed a Swiss-Webster mouse myenteric neuron culture and examined their electrophysiological properties by patch-clamp techniques and determined the mechanism for morphine-induced decrease in neuronal excitability. Isolated neurons in culture were confirmed by immunostaining with pan-neuronal marker, β-III tubulin and two populations were identified by calbindin and calretinin staining. Distinct neuronal populations were further identified based on the presence and absence of an afterhyperpolarization (AHP). Cells with AHP expressed greater density of sodium currents. Morphine (3 µM) significantly reduced the amplitude of the action potential, increased the threshold for spike generation but did not alter the resting membrane potential. The decrease in excitability resulted from inhibition of sodium currents. In the presence of morphine, the steady-state voltage dependence of Na channels was shifted to the left with almost 50% of channels unavailable for activation from hyperpolarized potentials. During prolonged exposure to morphine (two hours), action potentials recovered, indicative of the development of tolerance in single enteric neurons. These results demonstrate the feasibility of isolating mouse myenteric neurons and establish sodium channel inhibition as a mechanism for morphine-induced decrease in neuronal excitability.     

Effect of conditioning polarization of soma of giant neurons of mollusks on the mechanism of action-potential generation

To ascertain the properties of an excitable membrane of the soma of giant neurons of mollusks, experiments were carried out to study the effect of conditioning shift of the membrane potential on the mechanism of action-potential generation. The effect of conditioning was assessed from changes in the action-potential curve and its first derivative, as well as from the curve of transmembrane currents under voltage clamp conditions. It was found that a change in membrane potential evokes at least two reactions which have opposite effects on the mechanism of generation of action potentials. These reactions evidently have different time characteristics. One of these does not differ notably from the reaction recorded for other excitable structures, and is manifested in the activation (with hyperpolarization) or inactivation (with depolarization) of the mechanism generating action potentials. The other reaction contributes either to an increase (with depolarization) or a decrease (with hyperpolarization) in the efficiency of this mechanism. Conditioning polarization also has a marked effect on the system responsible for repolarization of the membrane during generation of action potentials. This effect is manifested in a change in the reaction of this system to tetraethylammonium ions. The specific membrane systems sustaining excitability and reacting to changes in the strength of the membrane's electrical field were found to be very inert. After a shift in the potential to a given stable level a rearrangement, lasting sometimes tens of seconds, takes place in the membrane.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 91–99, January–February, 1970.     

Voltage-gated currents and firing properties of embryonic Drosophila neurons grown in a chemically defined medium

This study reports the composition of a chemically defined medium (DDM1) that supports the survival and differentiation of neurons in dissociated cell cultures prepared from midgastrula stage Drosophila embryos. Cells with neuronal morphology that stain with a neural-specific marker are clearly differentiated by 1 day in vitro and can be maintained in culture for up to 2 weeks. Although the whole cell capacitance measurements from neurons grown in DDM1 were 5- to 10-fold larger than those of neurons grown in a conventional serum-supplemented medium, the potassium current densities were similar in the two growth conditions. A small but significant increase in the sodium current density was observed in the neurons grown in DDM1 compared with those in serum-supplemented medium. The majority of neurons grown in DDM1 fired either single or trains of action potentials in response to injection of depolarizing current. Contributing to the observed heterogeneity in the firing properties between individual neurons grown in DDM1 was heterogeneity in the levels of expression and gating properties of voltage-dependent sodium, calcium, and pottassium currents. The ability of embryonic Drosophila neurons to differentiate in a chemically defined medium and the fact that they are amenable to both voltage-clamp and current-clamp analysis makes this system well suited to studies aimed at understanding the mechanisms regulating expression of ion channels involved in electrical excitability. © 1995 John Wiley & Sons, Inc.     

Two patterns of bulbar neuronal response to microstimulation of locomotor and inhibitory brain stem sites

Synaptic responses (postsynaptic potentials and action potentials) were evoked in mesencephalic decerebellated cats by stimulating pontine bulbar locomotor and inhibitory sites (LS and IS, respectively) with a current of not more than 20 µA in "medial" and "lateral" neurons of the medulla. Some neurons even produced a response to presentation of single (actually low — 2–5 Hz — frequency) stimuli. The remaining cells responded to stimulation at a steady rate of 30–60 Hz only. Both groups of medial neurons were more receptive to input from LS. Lateral neurons responding to even single stimuli reacted more commonly to input from LS and those responding to steady stimulation only to input from IS. Many neurons with background activity (whether lateral or medial) produced no stimulus-bound response, but rhythmic stimulation either intensified or inhibited such activity. This response occurs most commonly with LS stimulation. Partial redistribution of target neurons in step with increasing rate of presynaptic input may play a major part in control of motor activity.Institute for Research into Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 257–266, March–April, 1990.     

Electrophysiology of identified neurosecretory and non-neurosecretory cells in the cockroach pars intercerebralis

Two cell types can be distinguished with intracellular recording from the pars intercerebralis of the American cockroach (Periplaneta americana). The first type, which corresponds morphologically to the medial neurosecretory cell, always had spontaneously occurring, overshooting action potentials. These action potentials are probably endogenously produced. Tetrodotoxin experiments revealed that sodium is the dominant ion of the action potential. The action potentials are followed by a relatively long after-hyperpolarization. The input resistance of these cells ranged from 120 to 390 M omega. A mathematical model, based on cellular morphology and response to current pulses, revealed a membrane time constant of about 100 msec and an axonal:somatic conductance ratio of approximately 13. Area-specific membrane resistance was estimated at 33 k omega cm2. These cells also often had reversible and spontaneous inhibitory postsynaptic potentials. The second cell type, which is non-neurosecretory, never produced spontaneous action potentials and rarely had synaptic potentials. Action potentials could be evoked by current injection into the cell body or by extracellular stimulation of their axons in the posteroventral portion of the the protocerebrum. These action potentials also depend on sodium ions. Their input resistance ranged from 16 to 35 M omega. They had a membrane time constant of approximately 15 msec and an axonal:somatic conductance ratio of about 9. Their area specific membrane resistance was estimated at 14 k omega cm2.     

A putative cation channel, NCA-1, and a novel protein, UNC-80, transmit neuronal activity in C. elegans

Voltage-gated cation channels regulate neuronal excitability through selective ion flux. NALCN, a member of a protein family that is structurally related to the α1 subunits of voltage-gated sodium/calcium channels, was recently shown to regulate the resting membrane potentials by mediating sodium leak and the firing of mouse neurons. We identified a role for the Caenorhabditis elegans NALCN homologues NCA-1 and NCA-2 in the propagation of neuronal activity from cell bodies to synapses. Loss of NCA activities leads to reduced synaptic transmission at neuromuscular junctions and frequent halting in locomotion. In vivo calcium imaging experiments further indicate that while calcium influx in the cell bodies of egg-laying motorneurons is unaffected by altered NCA activity, synaptic calcium transients are significantly reduced in nca loss-of-function mutants and increased in nca gain-of-function mutants. NCA-1 localizes along axons and is enriched at nonsynaptic regions. Its localization and function depend on UNC-79, and UNC-80, a novel conserved protein that is also enriched at nonsynaptic regions. We propose that NCA-1 and UNC-80 regulate neuronal activity at least in part by transmitting depolarization signals to synapses in C. elegans neurons.