Effects of tetraethylammonium and 4-aminopyridine on the plateau potential of circular myometrium from the pregnant rat

In the pregnant rat, spontaneous electrical activity of circular muscle (CM) changes from single, plateau-type action potentials at early and mid-term to repetitive spike trains at term. To examine mechanisms underlying the plateau, we studied the effects of potassium channel blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on membrane potentials in CM from rats on gestation Days 14, 15, 16, 21 (term). Apparent membrane conductance was measured at rest and during the plateau in Day 14 muscles with and without TEA. 4-AP depolarized the resting membrane on all gestation days. Therefore, a direct action of 4-AP on plateau configuration could not be separated from an indirect effect of depolarization. TEA did not affect the resting potential but increased action potential size and depolarization rate on all gestation days. On Day 16, TEA reduced plateau amplitude, unmasking small, repetitive depolarizations. D-600 decreased plateau amplitude and duration and attenuated these effects of TEA. Plateau conductance increased initially then decreased before membrane repolarization. Membrane conductance and outward rectification during the plateau were reduced by TEA. The plateau potential may result from an outwardly rectifying TEA-sensitive current combined with a slow inward current, the plateau magnitude being determined by the relative intensity of each current.     

Mechanisms underlying burst generation of the pyloric muscle in the mantis,shrimp, Squilla oratoria

The pyloric constrictor muscles of the stomach in Squilla can generate spikes by synaptic activation via the motor nerve from the stomatogastric ganglion. Spikes are followed by slow depolarizing afterpotentials (DAPs) which lead to sustained depolarization during a burst of spikes. 1. The frequency of rhythmic bursts induced by continuous depolarization is membrane voltage-dependent. A brief depolarizing or hyperpolarizing pulse can trigger or terminate bursts, respectively, in a threshold-dependent manner. 2. The conductance increases during the DAP response. The amplitude of DAP decreases by imposed depolarization, whereas it increases by hyperpolarization. DAPs from successive spikes sum to produce a sustained depolarizing potential capable of firing a burst. 3. The spike and DAP are reduced in amplitude by decreasing [Ca]o, enhanced by Sr2+ or Ba2+ substituted for Ca2+, and blocked by Co2+ or Mn2+. DAPs are selectively blocked by Ni2+, and the spike is followed by a hyperpolarizing afterpotential. 4. The spike and DAP are prolonged by intracellular injection of the Ca2+ chelator EGTA. A hyperpolarizing afterpotential is abolished by EGTA and enhanced by increasing [Ca]o. The DAP is diminished in Na(+)-free saline and reduced by tetrodotoxin. 5. It is concluded that the muscle fiber is endowed with endogenous oscillatory properties and that the oscillatory membrane events result from changes of a voltage- and time-dependent conductance to Ca2+ and Na+ and a Ca2+ activated conductance to K+.     

Dependence of pituitary hormone secretion on the pattern of spontaneous voltage-gated calcium influx. Cell type-specific action potential secretion coupling.

In excitable cells, voltage-gated calcium influx provides an effective mechanism for the activation of exocytosis. In this study, we demonstrate that although rat anterior pituitary lactotrophs, somatotrophs, and gonadotrophs exhibited spontaneous and extracellular calcium-dependent electrical activity, voltage-gated calcium influx triggered secretion only in lactotrophs and somatotrophs. The lack of action potential-driven secretion in gonadotrophs was not due to the proportion of spontaneously firing cells or spike frequency. Gonadotrophs exhibited calcium signals during prolonged depolarization comparable with signals observed in somatotrophs and lactotrophs. The secretory vesicles in all three cell types also had a similar sensitivity to voltage-gated calcium influx. However, the pattern of action potential calcium influx differed among three cell types. Spontaneous activity in gonadotrophs was characterized by high amplitude, sharp spikes that had a limited capacity to promote calcium influx, whereas lactotrophs and somatotrophs fired plateau-bursting action potentials that generated high amplitude calcium signals. Furthermore, a shift in the pattern of firing from sharp spikes to plateau-like spikes in gonadotrophs triggered luteinizing hormone secretion. These results indicate that the cell type-specific action potential secretion coupling in pituitary cells is determined by the capacity of their plasma membrane oscillator to generate threshold calcium signals.     

Cesium blockade of delayed outward currents and electrically induced pacemaker activity in mammalian ventricular myocardium

The effects of Cs+, 5-25 mM, were studied in cat and guinea pig papillary muscles using voltage clamp and current clamp techniques. In solutions containing normal K+, the major effects of Cs+ were depolarization of the resting potential and reduction of the delayed outward current (ixl) between -80 and -20 mV. Both inward and outward portions of the isochronal current voltage relation (l-s clamps) were reduced by extracellular Cs+. This resulted in a substantial reduction of inward rectification and, by subtraction from the normal I-V relationship, the definition of a Cs+-sensitive component of current. Under current clamp conditions, 5-10 mM Cs+ produced a dose-dependent slowing of repetitive firing induced by depolarization. At higher concentrations (25 mM) the resting potential was depolarized and repetitive activity could not be induced by further depolarization. However, release of hyperpolarizing pulses was followed by prolonged bursts of repetitive action potentials, suggesting partial reversal of blockade or participation of another pacemaker process. The experimental results and a numerical simulation show that under readily attainable conditions, reduction in an outward pacemaker current may slow pacemaker activity.     

CRH-induced electrical activity and calcium signalling in pituitary corticotrophs

Pituitary corticotroph cells generate repetitive action potentials and associated Ca2+ transients in response to the agonist corticotropin releasing hormone (CRH). There is indirect evidence suggesting that the agonist, by way of complex intracellular mechanisms, modulates the voltage sensitivity of the L-type Ca2+ channels embedded in the plasma membrane. We have previously constructed a Hodgkin-Huxley-type model of this process, which indicated that an increase in the L-type Ca2+ current is sufficient to generate repetitive action potentials (LeBeau et al. (1997). Biophys. J.73, 1263-1275). CRH is also believed to inhibit an inwardly rectifying K+ current. In this paper, we have found that a CRH-induced inhibition of the inwardly rectifying K+ current increases the model action potential firing frequency, [Ca2+]i transients and membrane excitability. This dual modulatory action of CRH on inward rectifier and voltage-gated Ca2+ channels better describes the observed CRH-induced effects. This structural alteration to the model along with parameter changes bring the model firing frequency in line with experimental data. We also show that the model exhibits experimentally observed bursting behaviour, where the depolarization spike is followed by small oscillations in the membrane potential.     

Cardiac pacemaker mechanisms in the ostracod crustacean Vargula hilgendorfii

The heart of the ostracod crustacean Vargula hilgendorfii has a single intrinsic neuron that morphologically appears to innervate the myocardium. We, therefore, examined the heart activity electrophysiologically to determine whether the heartbeat is neurogenic. Each heartbeat is associated with a myocardial action potential composed of a spike potential followed by a plateau potential. The frequency of the action potential is not stable but changes successively over a wide range. The action potential is not preceded by a pacemaker potential and has an inflection in its rising phase. The myocardial cells couple electrically and fire almost simultaneously. The frequency of the action potential was unchanged by injection of depolarizing or hyperpolarizing current into the myocardium. However, slow oscillatory potentials appeared during the depolarization and its frequency was higher with increasing current intensity. Application of 1-microM tetrodotoxin (TTX) depolarized the myocardial membrane and completely prevented the action potential. During this depolarization, slow oscillatory potentials often appeared spontaneously. These results suggest that, although the myocardium has a property of conditional oscillator, the heartbeat is driven by the single cell cardiac ganglion that has both pacemaker and motor functions.     

The functional organization of the crayfish lamina ganglionaris

The functional properties of the multicolumnar interneurons of the crayfish lamina ganglionaris were examined by intracellular recording and the cell structures were revealed with the aid of Lucifer yellow or horseradish peroxidase iontophoresis. The multicolumnar monopolar cell M5 responds to a light pulse with a depolarizing compound EPSP and a burst of action potentials. Both the EPSP amplitude and the spike rate decay toward a lower level plateau in less than 200 ms after light onset. M5 is subject to surround inhibition, which is associated with a compound IPSP and net hyperpolarization of the membrane potential. Direct depolarization of M5 may provide a weak excitatory drive to medullary sustaining fibers (SF). Tangenital-cell type 1 (Tan1) has a broad expanse of neurites in the lamina (covering 10 to 15 cartridges) and a much narrower projection in the medulla (1 to 3 cartridges). The response to a light pulse has a long latency consistent with a polysynaptic receptor to Tan1 pathway. The response consists of a nearly rectangular hyperpolarization. Light 'off' elicits a depolarization and a burst of impulses. The polarity of the 'on' response can be reversed by hyperpolarizing the membrane by 23 mV. The receptive field is broad and the intensity-response function exceeds 4 log units. Direct hyperpolarization of Tan1 provides a strong excitatory signal to medullary SFs both in the dark and in the presence of illumination. We propose that Tan1 provides the principal steady-state excitatory drive to the SFs. Tangential-cell type 2 (Tan2) is distinguished from Tan1 by the extent and shape of the lamina process, which is a vertically oriented neurite spanning most of the lamina in a single plane. Functionally, Tan2 is similar in most respects to Tan1, but the response latency is much shorter, comparable to that of monopolar cells. T-cells may exhibit spontaneous impulse activity in the dark which is inhibited by a short latency hyperpolarizing light response. The receptive field, which is about 2 X larger than that of the columnar monopolar cells, is correlated with a small but multicolumnar dendritic arbor in the lamina. Since T-cells are aminergic, it is possible that the amines are normally released in the dark. A single amacrine cell was fully characterized. It exhibited a short latency hyperpolarizing response to light onset and a strong depolarizing 'off' response.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of membrane polarization on contractile threshold and time course of prolonged contractile responses in skeletal muscle fibers

Short muscle fibers (less than 1.5 mm) from the m. lumbricalis IV digiti of Rana pipiens were voltage-clamped at -100 mV with a two-microelectrode technique, in normal Ringer's solution containing 10(-6) g/ml tetrodotoxin. The activation curve relating peak tension to membrane potential could be shifted toward more negative or less negative potential values by hyperpolarizing or depolarizing the fiber membrane to -130, -120, or -70 mV, respectively, which indicates that contractile threshold depends on the fiber membrane potential. Long (greater than 5 s) depolarizing (90 mV) pulses induce prolonged contractile responses showing a plateau and a rapid relaxation phase similar to K contractures. Conditioning hyperpolarizations prolong the time course of these responses, while conditioning depolarizations shorten it. The shortening of the response time course, which results in a decrease of the area under the response, is dependent on the amplitude and duration of the conditioning depolarization. Depending on the magnitude and duration, a conditioning depolarization may also reduce peak tension. When the area under the response is reduced by 50%, the level of membrane potential also affects the repriming rate. During repriming, peak tension is restored before the contracture area. Thus, when peak tension is reprimed to 80%, the area is reprimed by 50% of its normal value. Repriming has a marked temperature dependency with a Q10 higher than 4. These results are compatible with the idea that an inactivation process, voltage and time dependent, regulates the release of calcium from the sarcoplasmic reticulum during these responses.     

Theoretical reconstruction of myotonia and paralysis caused by incomplete inactivation of sodium channels.

Muscle fibers from individuals with hyperkalemic periodic paralysis generate repetitive trains of action potentials (myotonia) or large depolarizations and block of spike production (paralysis) when the extracellular K+ is elevated. These pathologic features are thought to arise from mutations of the sodium channel alpha subunit which cause a partial loss of inactivation (steady-state Popen approximately 0.02, compared to < 0.001 in normal channels). We present a model that provides a possible mechanism for how this small persistent sodium current leads to repetitive firing, why the integrity of the T-tubule system is required to produce myotonia, and why paralysis will occur when a slightly larger proportion of channels fails to inactivate. The model consists of a two-compartment system to simulate the surface and T-tubule membranes. When the steady-state sodium channel open probability exceeds 0.0075, trains of repetitive discharges occur in response to constant current injection. At the end of the current injection, the membrane potential may either return to the normal resting value, continue to discharge repetitive spikes, or settle to a new depolarized equilibrium potential. This after-response depends on both the proportion of noninactivating sodium channels and the magnitude of the activity-driven K+ accumulation in the T-tubular space. A reduced form of model is presented in which a two-dimensional phase-plane analysis shows graphically how this diversity of after-responses arises as extracellular [K+] and the proportion of noninactivating sodium channels are varied.     

A voltage-dependent persistent sodium current in mammalian hippocampal neurons

Currents generated by depolarizing voltage pulses were recorded in neurons from the pyramidal cell layer of the CA1 region of rat or guinea pig hippocampus with single electrode voltage-clamp or tight-seal whole-cell voltage-clamp techniques. In neurons in situ in slices, and in dissociated neurons, subtraction of currents generated by identical depolarizing voltage pulses before and after exposure to tetrodotoxin revealed a small, persistent current after the transient current. These currents could also be recorded directly in dissociated neurons in which other ionic currents were effectively suppressed. It was concluded that the persistent current was carried by sodium ions because it was blocked by TTX, decreased in amplitude when extracellular sodium concentration was reduced, and was not blocked by cadmium. The amplitude of the persistent sodium current varied with clamp potential, being detectable at potentials as negative as -70 mV and reaching a maximum at approximately -40 mV. The maximum amplitude at -40 mV in 21 cells in slices was -0.34 +/- 0.05 nA (mean +/- 1 SEM) and -0.21 +/- 0.05 nA in 10 dissociated neurons. Persistent sodium conductance increased sigmoidally with a potential between -70 and -30 mV and could be fitted with the Boltzmann equation, g = gmax/(1 + exp[(V' - V)/k)]). The average gmax was 7.8 +/- 1.1 nS in the 21 neurons in slices and 4.4 +/- 1.6 nS in the 10 dissociated cells that had lost their processes indicating that the channels responsible are probably most densely aggregated on or close to the soma. The half-maximum conductance occurred close to -50 mV, both in neurons in slices and in dissociated neurons, and the slope factor (k) was 5-9 mV. The persistent sodium current was much more resistant to inactivation by depolarization than the transient current and could be recorded at greater than 50% of its normal amplitude when the transient current was completely inactivated. Because the persistent sodium current activates at potentials close to the resting membrane potential and is very resistant to inactivation, it probably plays an important role in the repetitive firing of action potentials caused by prolonged depolarizations such as those that occur during barrages of synaptic inputs into these cells.     

The action potential in the smooth muscle of the guinea pig taenia coli and ureter studied by the double sucrose-gap method

The configuration of the electrotonic potential and the action potential observed by the double sucrose-gap method was similar to that observed with a microelectrode inserted into a cell in the center pool between the gaps. In the taenia and the ureter, the evoked spike was larger in low Na or in Na-free (sucrose substitute) solution than in normal solution. However, the plateau component in the ureter was suppressed in the absence of Na. In Ca-free solution containing Mg (3–5 mM) and Na (137 mM), the membrane potential and membrane resistance were normal, but no spike could be elicited in both the taenia and ureter. Replacement of Ca with Sr did not affect the spike in the taenia, nor the spike component of the ureter but prolonged the plateau component. The prolonged plateau disappeared on removal of Na, while repetitive spikes could still be evoked. It was concluded that the spike activity in the taenia and in the ureter of the guinea pig is due to Ca entry, that the plateau component in the ureter is due to an increase in the Na conductance of the membrane, and that both mechanisms, for the spike and for the plateau, are separately controlled by Ca bound in the membrane.     

Acceleratory Synapses on Pacemaker Neurons in the Heart Ganglion of a Stomatopod, Squilla oratoria

The pacemaker neurons of the heart ganglion are innervated from the CNS through two pairs of acceleratory nerves. The effect of acceleratory nerve stimulation was examined with intracellular electrodes from the pacemaker cells. The major effects on the pacemaker potential were an increase in the rate of rise of the spontaneous depolarization and in the duration of the plateau. The aftereffect of stimulation could last for minutes. No clear excitatory postsynaptic potential (EPSP) was observed, however. On high frequency stimulation, a small depolarizing response (the initial response) was sometimes observed, but the major postsynaptic event was the following slow depolarization, or the enhancement of the pacemaker potential (the late response). With hyperpolarization the initial response did not significantly change its amplitude, but the late response disappeared, showing that the latter has the property of the local response. The membrane conductance did not increase with acceleratory stimulation. The injection of depolarizing current increased the rate of rise of the spontaneous depolarization, but only slightly in comparison with acceleratory stimulation, and did not increase the burst duration. It is concluded that the acceleratory effect is not mediated by the EPSP but is due to a direct action of the transmitter on the pacemaker membrane.     

TheBulla ocular circadian pacemaker

In an effort to understand the cellular basis of entrainment of circadian oscillators we have studied the role of membrane potential changes in the neurons which comprise the ocular circadian pacemaker of Bulla gouldiana in mediating phase shifts of the ocular circadian rhythm. We report that: 1. Intracellular recording was used to measure directly the effects of the phase shifting agents light, serotonin, and 8-bromo-cAMP on the membrane potential of the basal retinal neurons. We found that light pulses evoke a transient depolarization followed by a smaller sustained depolarization. Application of serotonin produced a biphasic response; a transient depolarization followed by a sustained hyperpolarization. Application of a membrane permeable analog of the intracellular second messenger cAMP, 8-bromo-cAMP, elicited sustained hyperpolarization, and occasionally a weak phasic depolarization. 2. Changing the membrane potential of the basal retinal neurons directly and selectively with intracellularly injected current phase shifts the ocular circadian rhythm. Both depolarizing and hyperpolarizing current can shift the phase of the circadian oscillator. Depolarizing current mimics the phase shifting action of light, while hyperpolarizing current produces phase shifts which are transposed approximately 180 degrees in circadian time to depolarization. 3. Altering BRN membrane potential with ionic treatments, depolarizing with elevated K+ seawater or hyperpolarizing with lowered Na+ seawater, produces phase shifts similar to current injection. 4. The light-induced depolarization of the basal retinal neurons is necessary for phase shifts by light. Suppressing the light-induced depolarization with injected current inhibits light-induced phase shifts. 5. The ability of membrane potential changes to shift oscillator phase is dependent on extracellular calcium. Reducing extracellular free Ca++ from 10 mM to 1.3 X 10(-7) M inhibits light-induced phase shifts without blocking the photic response of the BRNs. The results indicate that changes in the membrane potential of the pacemaker neurons play a critical role in phase shifting the circadian rhythm, and imply that a voltage-dependent and calcium-dependent process, possibly Ca++ influx, shifts oscillator phase in response to light.     

Membrane and firing properties of avian medial vestibular nucleus neuronsin vitro

The intrinsic membrane and firing properties of medial vestibular nucleus (MVN) neurons were investigated in slices of the chick brainstem using intracellular recording and current injection. Avian MVN neurons fired spontaneous action potentials with very regular interspike intervals. The rapid repolarization of all action potentials was followed by an after-hyperpolarization. Intracellular injection of steps of hyperpolarizing current revealed both an inward rectification of the membrane potential during the step and a rebound depolarization following the offset of the step. In some neurons, the rebound depolarization resulted in bursts of action potentials. Steps of depolarizing current applied to spontaneously active neurons evoked increases in firing rate that were higher at the onset of the step than during the steady-state response. The relationship between current and firing rate was linear. The membrane and firing properties of avian MVN neurons were distributed continuously across the population of recorded neurons. These properties appear identical to those of rodent MVN neurons, suggesting that the composition and distribution of ion channels in the MVN neuronal membrane has been highly conserved across vertebrate species.Abbreviations MVN medial vestibular nucleus - VOR vestibulo-ocular reflex - AHP after-hyperpolarization     

Effects of several sea anemone and scorpion toxins on excitability and ionic currents in the giant axon of the cockroach

The membrane effects of 4 sea anemone and 6 scorpion toxins have been studied under current clamp and voltage clamp conditions. Micromolar concentrations of the purified toxins were applied externally on single giant axons of the american cockroach. Periplaneta americana in a double oil-gap arrangement and the effects on the resting potential, action potential and underlying currents analysed. The 4 sea anemone toxins (Condylactis toxin, Anemonia toxin 2, Anthopleurin toxin A and Parasicyonis toxin) were found to considerably prolong the action potential. This effect is frequency dependent and long plateau spikes (100-500 ms in duration) are consistently seen for frequencies lower than 0.2 Hz. This effect is due to a considerable delay in the turning-off of the sodium current during square membrane depolarizations associated, for large concentrations, with a decrease in the potassium conductance. Toxin effects on the sodium current are not prevented by pretreatment with STX. From the 4 purified toxins extracted from the venom of the scorpion, Androctonus australis Hector, 3 (Mammal toxins 1 and 2 and crustacean toxin) were found to have sea anemone toxin like effects and to induce long duration plateau action potentials. As for sea anemone toxins, this effect is due to a lengthening of the falling phase of the sodium current associated with a small decrease in the potassium conductance. The 4th toxin (insect toxin or ITAaH) depolarizes the membrane and induces repetitive firing of short action potentials.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiology of the flounder heart (Platichthys flesus)—the effect of agents which modify transmembrane ion transport

1. A sucrose gap system was used to record action potentials and mechanical responses of flounder heart.2. Diltiazem eliminated mechanical responses and strongly inhibited the action potential plateau while nifedipine only slightly reduced cardiac contractions without significantly changing the action potential.3. Verapamil slightly hyperpolarized flounder heart but was without effect on either the action potential or mechanical activity except at very high concentrations.4. Lanthanum was ineffective at 2 mM on flounder heart, but manganese at 3 mM substantially inhibited electrical and mechanical responses accompanied by a small hyperpolarization. Substitution of manganese for calcium abolished all flounder cardiac activity.5. BAY K 8644 enhanced cardiac force and enhanced the action potential plateau while depolarizing the preparations. Calcium-free salines abolished heart contractions and the action potential plateau while the spike phase persisted.6. Low sodium salines enhanced while sodium-free salines abolished all heart activity as did tetrodotoxin above I μM. Tetrodotoxin abolished the action potential spike leaving only a small plateau phase.7. Substituting lithium for sodium hyperpolarized the heart, enhanced contractions and prolonged the action potential plateau. Ouabain enhanced cardiac activity and depolarized the heart but ferosemide was without effect on either electrical or mechanical activity.8. TEA at 6 mM had a modest positive inotropic effect and negative chronotropic effect on the heart while the action potential plateau phase was enhanced.9. These results indicate that extracellular sodium and calcium are crucial in flounder heart electrogenesis but such a major role for potassium could not be established.     

Effects of high and low doses of vitamins A and E on the excitability of frog cardiomyocytes

The effects of complex vitamins A and E on electrophysiological characteristics was investigated on frog cardiomyocytes. Large doses of vitamins A and E decreased the steepness of the action potential (AP) front, decreased the spike amplitude, shortened the plateau, decreased the steepness in the last phase of AP-repolarization, and decreased the rest potential level but considerably increased overshoot. The Ap-duration decreased noticeably. Small doses of vitamins decreased the spike amplitude, shortened the plateau, decreased the Ap-duration. We assume that complex of vitamins A and E can affect the cardiomyocyte membrane transport function, mainly due to the suppression of the slow membrane channels. The AP-front increase is less steep under the influence of vitamins. It is shown that the 0-phase depolarization speed decreases due to the inhibition of sodium channels.     

Spiking properties of olfactory receptor cells in the slice preparation

The whole-cell, patch clamp [corrected] method was applied to olfactory receptor cells in slice preparations made from bullfrog olfactory epithelium. Under voltage-clamp conditions, olfactory receptor cells showed a transient inward current followed by a steady outward current in response to depolarizing voltage steps, as has been shown in the isolated preparation. The input resistance was 5.4 +/- 3.9 GOmega and capacitance 21.9 +/- 9.7 pF. Under current-clamp conditions, depolarization of cells by current injection induced action potentials. In 13 out of 20, spike generation was repetitive with a maximum frequency of 24 Hz. The frequency of the repetitive discharges increased as the injected current was increased. The relationship between the size of the injected current and firing frequency could be well fitted by the Michaelis-Menten equation, indicating that the spike generation site lacks the non-linear boosting system. The slice preparation developed here would provide a powerful tool to study the spike encoding system of the olfactory receptor cells.     

A fully coupled transient excited state model for the sodium channel

Summary The axon membrane is simulated by standard Hodgkin-Huxley leakage and potassium channels plus a coupled transient excited state kinetic scheme for the sodium channel. This scheme for the sodium channel is as proposed previously by the author. Simultations are presented showing the form of the action potential, threshold behavior, accommodation, and repetitive firing. It is seen that the form of the individual action potential, its all-or-none nature, and its refractory period are well simulated by this model, as they are by the standard Hodgkin-Huxley model. However, the model differs markedly from the Hodgkin-Huxley model with respect to repetitive firing and accommodation to stimulating currents of slowly rising intensity, in ways that are anomn to be related to those features of the sodium inactivation which are anomalous to the H-H model. The tendency for repetitive firing is highly dependent on that parameter which primarily determintes the existence of the inactivation shift in voltage clamp experiments, in such a way that the more pronounced the inactivation shift, the less the tendency for repetitive firing,. The tendency for accommodation is highly dependent on that parameter which primarily determines the “τ_c − τ_h” separation, in such a way that the greater the separation the greater the tendency for the membrane to accommodate without firing action potentials to a slowly rising current.     

Tetrodotoxin-resistant electric activity in chick skeletal muscle cells differentiated in vitro

The embryonic chick skeletal muscle cells differentiated in cell culture from trypsin-dissociated myoblasts produce a spike response which is tetrodotoxin-sensitive. It has been found that many cells also produce a plateau response which is resistant to tetrodotoxin. The plateau response frequently occurs even in the muscle cells which do not normally exhibit the spike response. During the plateau response membrane resistance is greatly reduced below its resting value. The current-voltage relation in muscle cells with the plateau response is always S-shaped. It is suggested that the plateau arises from a voltage-dependent increase in permeability to external cations whose influx produce the maintained depolarization, and from low level of repolarizing potassium outflux. The plateau response is sensitive to manganese ions. This finding, together with resistibility to tetrodotoxin, suggests that calcium ions are the dominant carriers for the depolarizing current.