Inward rectification by hyperpolarization-activated Na current in the marine ciliate Euplotes vannus

Summary The ionic mechanisms underlying inward or anomalous rectification have been studied in the marine hypotrichous ciliate Euplotes vannus. Inward-current pulses of moderate amplitude elicited time-dependent rectification that started from a hyperpolarization peak and was expressed as a depolarizing sag towards rest. Voltage-clamp analysis showed that this depolarization is caused by the activation of a complex inward current that does not inactivate with time. The current is carried by a major Na and a minor K component. The Na-current component has been identified by its concentration-dependent reduction in low extra-cellular Na solutions and the capability of Li²⁺ as Na substitute to carry the current, though with a slightly reduced amplitude. The K-current component has been isolated from the total current after the replacement of Na²⁺ within the experimental solution. It was blocked in media that contained 10 mmol/liter TEA, a well-known blocker for K inwardly rectifying currents. TEA was only effective at membrane potentials close to or negative to the potassium equilibrium potential. The inward current was reduced after the injection of the Ca chelator EGTA into the cell. Also the elimination of the ciliary membrane, by deciliating cells with ethanol, reduced the amplitude of the inwardly rectifying currents. Both experiments indicate a regulatory function of Ca²²⁺ in inward rectification.The author is grateful to Harald Mikoleit for technical assistance and preparing the figures and to Prof. W. Lueken for his critical comments. This work was supported by Deutsche Forschungsgemeinschaft, SFB 171, C7.     

Information processing by nonspiking interneurons: passive and active properties of dendritic membrane determine synaptic integration

Nonspiking interneurons control activities of postsynaptic cells without generating action potentials in the central nervous system of many invertebrates. Physiological characteristics of their dendritic membrane have been analyzed in previous studies using single electrode current- and voltage-clamp techniques. We constructed a single compartment model of an identified nonspiking interneuron of crayfish. Experimental results allowed us to simulate how the passive and active properties of the dendritic membrane influence the integrative processing of synaptic inputs. The results showed that not only the peak amplitude but also the time course of synaptic potentials were dependent on the membrane potential level at which the synaptic activity was evoked. When the synaptic input came sequentially, each individual input was still discernible at depolarized levels at which the membrane time constant was short due to depolarization-dependent membrane conductances. In contrast, synaptic potentials merged with each other to develop a sustained potential at hyperpolarized levels where the membrane behaved passively. Thus, synaptic integration in a single nonspiking interneuron depends on the value of membrane potential at which it occurs. This probably reflects the temporal resolution required for specific types of information processing.     

Electrophysiological properties of neurons of the red nucleus in rat brain slices

In experiments on rat brain slices, we carried out intracellular recording from neurons of the red nucleus (RN). Passive electrical properties of these neurons (input resistance, membrane time constant) were evaluated. We detected voltage-dependent rebound depolarization and time dependent inward rectification when passing hyperpolarizing pulses of current through the cell. Injections of depolarizing currents caused rhythmical firing of the neurons; the frequency of these firings depends upon the strength of injected current. Rhythmical firings were also characterized by rapid frequency adaptation when currents of different frequency were injected. Stimulation of regions of slices presumably corresponding to the decussion of the brachium conjunctivum mainly evoked EPSPs with a "fast" rise time in RN neurons. This suggests activation of synaptic input from the cerebellar nucleus interpositus. Stimulation of this same region sometimes evoked EPSP-IPSP mixtures and "pure" IPSPs in RN neurons.L. A. Orbeli Institute of Physiology, Armenian Academy of Sciences, Erevan. Translated from Neirofiziologiya, Vol. 23, No. 5, pp. 607–616, September–October, 1991.     

Thyrotropin-releasing hormone mimics descending slow synaptic potentials in rat spinal motoneurons

Thyrotropin-releasing hormone (TRH) produced a depolarization in lumbar motoneurons of neonatal rats. The depolarization by TRH persisted after extracellular Ca2+ was replaced by Mg2+ or Mn2+, indicating its direct action upon motoneurons. Stimulation of the ventral descending tract at the lower thoracic segment evoked slow excitatory postsynaptic potentials (e.p.s.ps) lasting 20-30 s in every motoneuron. Both the TRH-induced depolarization and descending slow e.p.s.p. were accompanied by a decrease in input conductance of motoneurons. When the membrane potential of the motoneuron was shifted, both the TRH-induced depolarization and slow e.p.s.p. became larger in amplitude during depolarization and smaller during hyperpolarization. However, they could not be reversed in polarity by hyperpolarization. During the depolarization of motoneuron produced by TRH application, the slow e.p.s.p. was markedly reduced in amplitude, suggesting the involvement of identical ionic mechanisms in the two responses. After incubation of the isolated spinal cord with antisera to TRH, the depolarizing response produced by TRH as well as the descending slow e.p.s.p. was greatly diminished. In contrast, monosynaptic reflexes evoked by dorsal root stimulation remained unchanged under this condition. These results suggest that TRH serves as a neurotransmitter mediating the descending slow e.p.s.p. in motoneurons.     

Interaction of penicillin and pentobarbital with inhibitory synaptic mechanisms in neocortex

In this study we characterized the responses of neocortical neurons to iontophoretically applied gamma-aminobutyric acid (GABA) and examined how these GABA responses as well as the inhibitory postsynaptic potentials (IPSPs) were affected by the presence of penicillin or pentobarbital. Intracellular recordings were obtained from slices of rat neocortex maintained in vitro; injection of the dye Lucifer yellow indicated that recordings were primarily from pyramidal neurons. Orthodromically evoked responses were always depolarizing at the cell's resting membrane potential. Such depolarizing responses could easily be reversed in polarity by depolarizing the cell 10-15 mV, suggesting that the response consisted partly of an IPSP. In some cases, depolarization unmasked a small, short-latency excitatory postsynaptic potential (EPSP). Responses to iontophoretically applied GABA were also depolarizing at rest. Biphasic hyperpolarizing-depolarizing responses were occasionally observed upon depolarization of the neuron. Bath application of penicillin (1.7-3.4 mM) decreased the amplitude of the IPSPs and increased their time to peak, an effect associated with the development of epileptiform activity. Penicillin also reduced the maximum response to iontophoretically applied GABA without affecting the dose required to obtain a half-maximal response, suggesting a noncompetitive antagonism. Pentobarbital (100-200 microM) prolonged the time course and increased the amplitude of the IPSPs while producing a leftward shift in the GABA charge-response relation. These results suggest that the convulsant penicillin and the anticonvulsant pentobarbital have opposing actions on GABAergic inhibition in the neocortex.     

Cholinergic transmission from mechanosensory afferents to an identified nonspiking interneuron in the crayfish Procambarus clarkii girard

Pharmacological properties of excitatory synaptic transmission from mechanosensory afferents to an identifiable nonspiking interneuron of crayfish were studied by drug perfusion experiments using acetylcholine (ACh) agonists and antagonists. Application of carbachol, a general agonist of ACh, caused sustained depolarization of the interneuron and a decrease in the peak amplitude of its excitatory synaptic response to sensory stimulation on the soma side. Similar depolarization was observed during application of carbachol under the low-Ca²⁺, high-Mg²⁺ condition. The peak amplitude was also reduced by application of nicotine and tetramethylammonium, both of which also caused sustained depolarization of the inter-neuron. By contrast, perfusion of muscarinic agonists, muscarine, oxotremorine and pilocarpine, reduced the peak amplitude without affecting the membrane potential of the interneuron. Perfusion of nicotonic antagonists of ACh, d-tubocurarine and hexamethonium, caused reduction of the peak amplitude without any change in the membrane potential. A muscarinic antagonist atropine was also effective in blocking the synaptic transmission but at higher concentration than d-tubocurarine. The results suggest that the ACh receptors on the nonspiking interneuron belong to a previously characterized class of crustacean cholinergic receptors resembling the nicotinic subtype of vertebrates.     

Hyperpolarization of a barnacle photoreceptor membrane following illumination

Membrane potential changes following illumination of a photoreceptor cell in the lateral ocellus of a barnacle (Balanus eburneus) were studied by means of intracellular recording and polarization techniques. Illumination produces a depolarizing response. When the illumination is terminated, the membrane potential temporarily becomes more negative than the resting potential prior to illumination. Although the amplitude of this postillumination hyperpolarization depends upon the intensity as well as the duration of the light pulse, the time course is fairly constant. The hyperpolarization is not associated with any significant membrane conductance increase and is abolished by 10^-5 M ouabain. It diminishes when the external Na or K ions are removed. An intracellular injection of Na ions produces a hyperpolarization similar to that following illumination. It is suggested that the postillumination hyperpolarization is produced by an electrogenic Na pump which is activated by the Na influx during illumination.     

Presynaptic inhibition in the cercal-afferent giant-interneurone synapses of the cockroach, Periplaneta americana L.

The occurrence of presynaptic control of synaptic transmission in the cercal-afferent giant-interneurone system of the cockroach was investigated. Reduction in amplitude (up to 50%, lasting about 200–250 ms) of the compound evoked EPSP followed repetitive (300 to 500 Hz) supra-threshold stimulation of cercal nerves XI. A similar but weaker depressive effect was detected on the unitary EPSP resulting from stimulation of an ipsilateral cercal mechanoreceptor.This inhibition is attributed to multisynaptic inhibitory pathways impinging upon presynaptic excitatory neurones. The involvement of chloride ions is suggested by the observation that both picrotoxin and chloride-deficient salines abolished the inhibitory phenomenon. Presynaptic mannitolgap recording from cercal nerve XI revealed a chloride-dependent hyperpolarization in response to repetitive conditioning stimulation. The time course of this response was similar to that of presynaptic inhibition. Bath-application of GABA (20 mM) produced a chloride-dependent hyperpolarization followed by a depolarization of the intraganglionic part of the cerca-afferents. GABA-induced hyperpolarization and electrically-induced presynaptic hyperpolarization were both reversed in low chloride saline (166 mM chloride). It is proposed that presynaptic modulation of acetyl-choline release occurs at the cercal-afferent giant-interneurone synapses. The role played by GABA is duscussed.     

Local interneurons and information processing in the olfactory glomeruli of the moth Manduca sexta

Intracellular recordings were made from the major neurites of local interneurons in the moth antennal lobe. Antennal nerve stimulation evoked 3 patterns of postsynaptic activity: (i) a short-latency compound excitatory postsynaptic potential that, based on electrical stimulation of the antennal nerve and stimulation of the antenna with odors, represents a monosynaptic input from olfactory afferent axons (71 out of 86 neurons), (ii) a delayed activation of firing in response to both electrical- and odor-driven input (11 neurons), and (iii) a delayed membrane hyperpolarization in response to antennal nerve input (4 neurons).Simultaneous intracellular recordings from a local interneuron with short-latency responses and a projection (output) neuron revealed unidirectional synaptic interactions between these two cell types. In 20% of the 30 pairs studied, spontaneous and current-induced spiking activity in a local interneuron correlated with hyperpolarization and suppression of firing in a projection neuron. No evidence for recurrent or feedback inhibition of projection neurons was found. Furthermore, suppression of firing in an inhibitory local interneuron led to an increase in firing in the normally quiescent projection neuron, suggesting that a disinhibitory pathway may mediate excitation in projection neurons. This is the first direct evidence of an inhibitory role for local interneurons in olfactory information processing in insects. Through different types of multisynaptic interactions with projection neurons, local interneurons help to generate and shape the output from olfactory glomeruli in the antennal lobe.Abbreviations AL antennal lobe - EPSP excitatory postsynaptic potential - GABA -aminobutyric acid - IPSP inhibitory postsynaptic potential - LN local interneuron - MGC macroglomerular complex - OB olfactory bulb - PN projection neuron - TES N-tris[hydroxymethyl]methyl-2-aminoethane-sulfonic acid     

Processing of sensory signals by a non-spiking neuron in the leech

The non-spiking neurons 151 are present as bilateral pairs in each midbody ganglion of the leech nervous system and they are electrically coupled to several motorneurons. Intracellular recordings were used to investigate how these neurons process input from the mechanosensory P neurons in isolated ganglia. Induction of spike trains (15 Hz) in single P cells evoked responses that combined depolarizing and hyperpolarizing phases in cells 151. The phasic depolarizations, transmitted through spiking interneurons, reversed at around -20 mV. The hyperpolarization had two components, both reversing at around -65 mV, and which were inhibited by strychnine (10 micromol l(-1)). The faster component was transmitted through spiking interneurons and the slower component through a direct P-151 interaction. Short trains (<400 ms) of P cell spikes (15 Hz) evoked the phasic depolarizations superimposed on the hyperpolarization, while long spike trains (>500 ms) produced a succession of depolarizations that masked the hyperpolarizing phase. The amplitude and duration of the hyperpolarization reached their maximum at the initial spikes in a train, while the depolarizations persisted throughout the duration of the stimulus train. Both phases of the response were relatively unaffected by the spike frequency (5-25 Hz). The non-spiking neurons 151 processed the sensory signals in the temporal rather than in the amplitude domain.     

Functional assay for GABA receptor subtypes of a cockroach giant interneuron.

gamma-Aminobutyric acid (GABA) receptors were examined in the cockroach central nervous system (CNS) using the single fiber-oil gap method applied to an identified giant interneuron. Short-lasting pressure application of 10 mM GABA developed a multiphasic response composed of a fast hyperpolarization followed by a transient depolarizing component and a stable hyperpolarization. This triphasic characteristic shape of the response was modified according to the dose of GABA injected or bath-applied and to the precise localization of the injection within the dendritic area. The transient depolarizing phase showed a negative reversal potential of -70 mV. Both hyperpolarizing phases reversed at a more negative level ranging to -80 mV. A positive shift of these values was caused by a decrease in external chloride concentration. Bath-application of 0.1 mM picrotoxin (Ptx) decreased the depolarizing phase which was progressively replaced by a stable hyperpolarization. The transient depolarizing component desensitized quickly and was the most sensitive phase to Ptx action. The Ptx-resistant response reversed at a mean value of -100 mV close to the equilibrium potential for potassium ions (EK+), suggesting that it was generated by a K(+)-channel coupled receptor. Although baclofen was unable to mimic the Ptx-resistant GABA response, the compound CGA 147823, known to bind with a high specificity to vertebrate GABAB receptors, has been successfully used to reproduce the Ptx-resistant GABA response. It is suggested that, in addition to GABA receptors linked to chloride channels, the insect CNS possesses GABA receptors sharing ionic characteristics of GABAB receptors especially those located in the vertebrate CNS, although they are insensitive to baclofen.     

Effects of rectification on synaptic efficacy.

We have investigated the effects of postsynaptic membrane properties on the shape of synaptic potentials generated by time-varying synaptic conductances. We used numerical simulation techniques to model cells of several different geometrical forms, from an isopotential sphere to a neuron with a soma and a dendritic tree. A variety of postsynaptic membrane properties were tested: (a) a passive resistance-capacitance membrane, (b) a membrane represented by the Hodgkin and Huxley (HH) equations, and (c) a membrane that was passive except for a delayed rectification represented by a voltage- and time-dependent increase in GK. In all cases we investigated the effects of these postsynaptic membrane properties on synaptic potentials produced by synaptic conductances that were fast or slow compared with the membrane time constant. In all cases the effects of postsynaptic rectification occurred on postsynaptic potentials of amplitudes as low as 1 mV. The HH model (compared with the passive model) produced an increased peak amplitude (from the increase in GNa) but a decreased half-width and a decreased time integral (from the increase in GK). These effects of the HH GK change were duplicated by a simple analytical rectifier model.     

Neural circuitry underlying linear representation of wind information in a nonspiking local interneuron of the cockroach

In the cercal system of the cockroach Periplaneta americana, primary sensory interneurons exhibiting a sharp directional sensitivity respond to wind in a linear manner whereas those exhibiting an omnidirectional sensitivity respond nonlinearly. For example, the wind-evoked response in an identifiable, nonspiking local interneuron, 101, which responds preferentially to wind from the left versus the right, is characterized exclusively by a differential first-order (linear) kernel. However, the slow potential response in a cercal giant interneuron, GI-1, is omnidirectional, and characterized by a second-order (nonlinear) kernel with an elongated depolarizing peak on the diagonal with two off-diagonal valleys. We here examined the neural circuitry underlying the linear and nonlinear representations of wind information by the deprivation of inputs from particular sets of cercal hair afferents. Electrical stimulation of the ipsilateral (related to the soma) cercal nerve elicited a depolarizing potential in 101, which was followed by delayed hyperpolarization. A continuous flow of 10^–4 M picrotoxin, which selectively blocked this delayed hyperpolarization, resulted in a significant change in the 101 response from linear to nonlinear. Because no frequency-doubling response was observed, the nonlinearity is due to signal compression (or rectification) that reflects the mechanical property of cercal afferents. This is consistent with the hypothesis that the linear representation in 101 is based on a subtraction process between two subsets of particular column hairs, whose best optimal directions are opposite to each other.Abbreviations GABA -aminobutyric acid - GI(s) giant interneuron(s) - GI-1, GI-2, GI-3, GI-4 giant interneuron 1,2,3,4 - ipsi ipsilateral - cont contralateral - MSE(s) mean square error(s)     

Electrophysiological and Theoretical Analysis of Depolarization-Dependent Outward Currents in the Dendritic Membrane of an Identified Nonspiking Interneuron in Crayfish

Depolarization-dependent outward currents were analyzed using the single-electrode voltage clamp technique in the dendritic membrane of an identified nonspiking interneuron (LDS interneuron) in situ in the terminal abdominal ganglion of crayfish. When the membrane was depolarized by more than 20 mV from the resting potential (65.0 ± 5.7 mV), a transient outward current was observed to be followed by a sustained outward current. Pharmacological experiments revealed that these outward currents were composed of 3 distinct components. A sustained component (I _s) was activated slowly (half rise time > 5 msec) and blocked by 20 mM TEA. A transient component (I _t1) that was activated and inactivated very rapidly (peak time < 2.5 msec, half decay time < 1.2 msec) was also blocked by 20 mM TEA. Another transient component (I _t2) was blocked by 100 M 4AP, activated rapidly (peak time < 10.0 msec) and inactivated slowly (half decay time > 131.8 msec). Two-step pulse experiments have revealed that both sustained and transient components are not inactivated at the resting potential: the half-maximal inactivation was attained at –21.0 mV in I _t1, and –38.0 mV in I _t2. I _s showed no noticeable inactivation. When the membrane was initially held at the resting potential level and clamped to varying potential levels, the half-maximal activation was attained at –36.0 mV in I _s, –31.0 mV in I _t1 and –40.0 mV in I _t2. The activation and inactivation time constants were both voltage dependent. A mathematical model of the LDS interneuron was constructed based on the present electrophysiological records to simulate the dynamic interaction of outward currents during membrane depolarization. The results suggest that those membrane conductances found in this study underlie the outward rectification of the interneuron membrane as well as depolarization-dependent shaping of the excitatory synaptic potential observed in current-clamp experiments.     

Tetrodotoxin--a sensitive component of the depolarizing response to GABA administration to the pyramidal neuron dendrites of the CA1 field of the hippocampus

The intracellular recording of CA1 neurons in mouse hippocampal slice preparation was used to study the properties of depolarizing responses to iontophoretically applied GABA to their apical dendrites. Reversal potential of depolarizing responses was dependent on parameters of injecting current. It was about -60 mV and - (45-55) mV when iontophoretic currents 40-60 nA and 8-20 nA were used respectively. Application of tetrodotoxin (0.1-0.5 microM) resulted in decrease in amplitude of depolarizing responses evoked by weak currents, increase in slope of plot, reflecting relationship between response amplitude and membrane potential, and hyperpolarizing shift of reversal potential. Blocking++ of synaptic transmission with low calcium solution did not produce such changes. These results suggest that GABA depolarizing responses have a potential-sensitive component due to activation of sodium channels.     

Ionic mechanisms underlying the responses of off-center bipolar cells in the carp retina. II. Studies on responses evoked by transretinal current stimulation

Transretinal current pulses flowing from the receptor side to the vitreous side of the retina cause transient release of transmitter from the photoreceptor terminals, and in off-center bipolar cells they evoke transient depolarizations with a brief (less than 1 ms) synaptic delay. Since it is known that the presence of Na+ in the external medium is not essential for this type of transmitter release, we used this procedure to examine the role of [Na+]o in the generation of light- evoked responses (hyperpolarizing to spot illumination in the receptive field center and depolarizing to an annulus in the surround) of this type of bipolar cell. When the cell membrane was steadily depolarized by current injection through the recording microelectrode, the depolarizing response evoked by the transretinal current pulses decreased in amplitude and reversed its polarity at above +45 mV. Conversely, the response amplitude increased when the cell was steadily hyperpolarized. The reversal potential seems to be lowered in low [Na+]o (28 mM). Removal of Na+ from the superfusate hyperpolarized the cell and both the light-evoked and current-evoked responses disappeared. From these observations, it is hypothesized that the hyperpolarizing center response of the off-center bipolar cells is a result of removal of sustained depolarization produced by sodium permeability increase.     

新生大鼠离体脊髓薄片侧角中间外侧核细胞的电生理特性

在新生大鼠离体脊髓薄片的中间外侧核作细胞内记录,研究细胞膜的静态与动态电生理特性。细胞的静息电位(RP)变动于-46—-70mV,膜的输入阻抗为108.3±67.9MΩ(X±SD,下同),时间常数9.9±5.6ms,膜电容138.6±124.2pF。用去极化电流进行细胞内刺激时,大部份细胞(85.4％)能产生高频率连续发放,其余细胞(15.6％)仅产生初始单个发放。胞内直接刺激引起的动作电位(AP)幅度为63.4±9.0mV,时程2.4±0.6ms,阈电位水平在RP基础上去极18.7±6.2mV。大部份细胞的锋电位后存在明显的超极化后电位,其幅度为5.1±2.7mV、持续90±31.8ms。刺激背根可在记录细胞引起EPSP或顺向AP,少数细胞尚出现IPSP。而刺激腹根则可引起逆向AP。     

Possible interaction between synaptic and pacemaker mechanisms of electrical activity in bursting neurons of Helix pomatia

Membrane hyperpolarization induced by short pulses of inward current, by stimulation of the anal nerve, which leads to the appearance of a long IPSP in the neuron, and developing during the appearance of spontaneous IPSPs in the neuron was investigated in neuron RPa1 ofHelix pomatia. Short-term hyperpolarization of the neuron membrane by an inward current (10 msec) led to the development of self-maintained (regenerative) membrane hyperpolarization lasting several seconds. The amplitude and duration of regenerative hyperpolarization increased with an increase in amplitude and duration of the pulse of inward current. The time course of IPSPs arising spontaneously in the neuron and in response to stimulation of the anal nerve was similar to that of regenerative hyperpolarization evoked by a pulse of inward current. It is suggested that regenerative hyperpolarization associated with activation of endogenous mechanisms of regulation of the bursting activity of the neuron may be due not only to short-term membrane hyperpolarization of the test neuron by the electric current, but also to hyperpolarization occurring during IPSP generation.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 1, pp. 67–74, January–February, 1981.     

Characteristics of long-duration inhibitory postsynaptic potentials in rat neocortical neuronsin vitro

The characteristics of long-duration inhibitory postsynaptic potentials (1-IPSPs) which are evoked in rat frontal neocortical neurons by local electrical stimulation were investigated with intracellular recordings from an in vitro slice preparation. Stimulation with suprathreshold intensities evoked 1-IPSPs with typical durations of 600-900 msec at resting membrane potential. Conductance increases of 15-60% were measured at the peak amplitude of 1-IPSPs (150-250 msec poststimulus). The duration of the conductance increases during 1-IPSPs displayed a significant voltage dependence, decreasing as the membrane potential was depolarized and increasing with hyperpolarization. The reversal potential of 1-IPSPs is significantly altered by reductions in the extracellular potassium concentration. Therefore it is concluded that 1-IPSPs in rat neocortical neurons are generated by the activation of a potassium conductance. 1-IPSPs exhibit stimulation fatigue. Stimulation with a frequency of 1 Hz produces a complete fatigue of the conductance increases during 1-IPSPs after approximately 20 consecutive stimuli. Recovery from this fatigue requires minutes. 1-IPSPs are not blocked by bicuculline but are blocked by baclofen.     

Persistent inward currents in cultured Retzius cells of the medicinal leech

Current-clamp studies of cultured leech Retzius cells revealed inward rectification in the form of slow voltage sags in response to membrane hyperpolarization. Sag responses were eliminated in Na⁺-free saline and blocked by Cs⁺, but not Ba²⁺. Voltage clamp experiments revealed a Cs⁺-sensitive inward current activated by hyperpolarization negative to −70 mV. Cs⁺ decreased the frequency of spontaneous impulses in Retzius cells of intact ganglia. Plateau potentials were evoked in Retzius cells following block of Ca²⁺ influx with Ni²⁺ and suppression of K⁺ currents with internal tetraethylammonium. Plateau potentials continued to be expressed with Li⁺ as the charge carrier, but were eliminated when Na⁺ was replaced with N-methyl-d-glucamine. A persistent Na⁺ current with similar pharmacology that activated positive to −40 mV and reached its peak amplitude near −5 mV was identified in voltage-clamp experiments. Inactivation of the persistent Na⁺ current was slow and incomplete. The current was revealed by slow voltage ramps and persisted for the duration of 5-s voltage steps. Persistent Na⁺ current may underlie Na⁺-dependent bursting recorded in neurons of intact ganglia exposed to Ca²⁺-channel blockers. Accepted: 22 September 1998