Appearance and maturation of voltage-dependent conductances in solitary spiking cells during retinal regeneration in the adult newt

Summary Electrical membrane properties of solitary spiking cells during newt (Cynops pyrrhogaster) retinal regeneration were studied with whole-cell patch-clamp methods in comparison with those in the normal retina.The membrane currents of normal spiking cells consisted of 5 components: inward Na⁺ and Ca⁺⁺ currents and 3 outward K⁺ currents of tetraethylammonium (TEA)-sensitive, 4-aminopyridine (4-AP)-sensitive, and Ca⁺⁺-activated varieties. The resting potential was about -40mV. The activation voltage for Na⁺ and Ca⁺⁺ currents was about -30 and -17 mV, respectively. The maximum Na⁺ and Ca⁺⁺ currents were about 1057 and 179 pA, respectively.In regenerating retinae after 19–20 days of surgery, solitary cells with depigmented cytoplasm showed slowrising action potentials of long duration. The ionic dependence of this activity displayed two voltage-dependent components: slow inward Na⁺ and TEA-sensitive outward K⁺ currents. The maximum inward current (about 156 pA) was much smaller than that of the control. There was no indication of an inward Ca⁺⁺ current.During subsequent regeneration, the inward Ca⁺⁺ current appeared in most spiking cells, and the magnitude of the inward Na⁺, Ca⁺⁺, and outward K⁺ currents all increased. By 30 days of regeneration, the electrical activities of spiking cells became identical to those in the normal retina. No significant difference in the resting potential and the activation voltage for Na⁺ and Ca⁺⁺ currents was found during the regenerating period examined.     

Ionic bases of action potentials in identified flatworm neurones

Summary The ionic bases for generation of action potentials in three types of identified multimodal neurones of the brain ofNotoplana acticola, a polyclad flatworm, were studied. The action potentials were generated spontaneously, in response to water-borne vibrations, or by intracellularly injected current pulses. At least three components comprise the depolarizing excitable phase of the action potentials: (a) a rapidly inactivating TTXsensitive Na⁺ component (Fig. 2); (b) a Ca⁺⁺ component that is unmasked by intracellular TEA⁺ (Figs. 4, 6, 7); (c) a TTX-resistant Na⁺ component (Fig. 8). Two K⁺ currents appear to account for the repolarization phase of the action potentials: (a) a rapid K⁺ current that is blocked by intracellular TEA⁺ (Figs. 4, 7, 8) and (b) a Ca⁺⁺ -activated K⁺ conductance that is blocked by Ca⁺⁺ and Ba⁺⁺ (Fig. 6). Ionic mechanisms in the generation of action potentials in the central multimodal neurones ofNotoplana pharmacologically resemble those in higher metazoans.Abbreviations TTX tetrodotoxin - TEA ⁺ tetraethylammonium ion - LY lucifer yellow - HRP horseradish peroxidase - BRA bilaterally reciprocally arrayed neurons - SC single contralaterally projecting - SIC single ipsilaterally and contralaterally projecting neurons - HAP hyperpolarizing after potential - AHP after hyperpolarization - EGTA ethyleneglycol-bis-(-amino-ethyl ester) N,N-tetra-acetic acid     

Electrophysiology of an Insect Heart

Bioelectric activity in single cells of the moth myocardium has been measured in situ with intracellular microelectrodes with particular reference to the bizarre ionic medium which bathes the tissues. Resting potentials averaged 47 mv, inside negative with respect to outside, despite a value of 11 mv calculated on the basis of transmembrane potassium concentration gradients. Action potentials overshoot as much as 12 mv in the virtual absence of extracellular sodium. Two "types" of action potentials have been recorded; one that resembles vertebrate atrial action potentials is found in the cephalic region of the tubular heart, and the other, similar in contour to vertebrate ventricular action potentials, is found in the areas posterior to the first abdominal segment. Histological sections indicate no structural differences between the two areas. Typical cardiac pacemaker type potentials occur but are not topographically localized. The effects of the omission from the perfusion fluid of the four major cationic constituents, Na⁺, K⁺, Ca⁺⁺ and Mg⁺⁺, on resting and action potentials may be summarized as: no effect, hyperpolarization, prolonged repolarization, and depolarization, respectively.     

A mutant of Paramecium with increased relative resting potassium permeability

Fast-2, a membrane mutant of Paramecium aurelia, is due to a single-gene mutation and has behavioral abnormalities. Intracellular recordings through changes of external solutions were made. The mutant membrane hyperpolarized when it encountered solutions with low K⁺ concentration. This hyperpolarization and other associated activities were best observed in Ca- or Na-solutions devoid of K⁺. Membrane potential was plotted against the concentration of K⁺ (0.5 to 16 mM) in solutions of fixed Na⁺ or Ca⁺⁺ concentration. The slopes of the curves for the mutant membrane were steeper than those for the wild type at the lower concentrations of K⁺. Inclusion of 2 mM tetraethylammonium chloride (TEA-Cl) counteracted the mutational effects. Spontaneous action potentials in Ba-solution and the electrically evoked action potentials in various solutions are normal in this mutant. We conclude that the resting permeability to K⁺ relative to the permeabilities to Na⁺ and Ca⁺⁺ has been increased by the mutation.     

Effects of different ions on resting polarization and on the mass receptor potential of carotid body chemosensors

The carotid body and its own nerve were removed from cats anesthetized with sodium pentobarbital and placed in an air gap system; the carotid body was bathed in modified Locke's solution equilibrated with 50% O₂ in N₂, pH 7.43 at 35°C. The sensory discharges, changes in “resting” receptor polarization and the mass receptor potential evoked by ACh or NaCN were recorded with nonpolarizable electrodes placed across the gap. Receptor potentials and sensory discharges evoked by ACh showed an appreciable increase in amplitude and frequency when the preparation was bathed in eserinized Locke. Eserine did not change appreciably the responses evoked by NaCN. Excessive depolarization elicited by either ACh or NaCN was accompanied by sensory discharge block. Removal of K⁺ ions from the bathing solution induced receptor hyperpolarization and an increase in the amplitude of the evoked receptor potentials. An increase of K⁺ concentration had the opposite effect. Reduction of Na⁺ or NaCl to one half, or total removal of this salt, induced an initial reduction and later disappearance of the sensory discharges, some receptor hyperpolarization and a reduction in the amplitude of the evoked receptor potentials. Reduction or removal of Ca⁺⁺ produced receptor depolarization, a marked depression of the evoked receptor potentials, an increase in the frequency of the sensory discharges and a reduction in the amplitude of the nerve action potentials. High Ca⁺⁺ or Mg⁺⁺ had little or no effect on action potential amplitude or resting polarization, but decreased sensory discharge frequency and the evoked receptor potentials. Total or partial replacement of Ca⁺⁺ with Mg⁺⁺ induced complex effects: (1) receptor depolarization which occurred in low Ca⁺⁺, was prevented by addition of Mg⁺⁺ ions; (2) the amplitude of the evoked receptor potentials was depressed; (3) the nerve discharge frequency was reduced as it was in high Mg⁺⁺ solutions; and (4) the amplitude of the nerve action potentials was reduced as it was in low Ca⁺⁺ solutions. Temperature had a marked effect on the chemoreceptors since a t high temperatures the receptors were depolarized and the discharge frequency increased. The baseline discharge and responses evoked by ACh or NaCN were depressed at low temperatures. The results are discussed in terms of possible receptor mechanisms influenced by the different ions.     

The penetration of some cations into muscle

The influx of Na⁺, K⁺, Rb⁺, and Cs⁺ into frog sartorius muscle has been followed. The results show that a maximum rate is found for K⁺, while Na⁺ and Cs⁺ penetrate much more slowly. Similar measurements with Ca⁺⁺, Ba⁺⁺, and Ra⁺⁺ show that Ba⁺⁺ penetrates at a rate somewhat greater than that of either Ca⁺⁺ or Ra⁺⁺. All these divalent cations, however, penetrate at rates much slower than do the alkali cations. The results obtained are discussed with reference to a model that has been developed to explain the different penetration rates for the alkali cations.     

Mediation of beta-adrenergic stimulated amylase release from mouse parotid gland

Amylase released from mouse parotid fragments by the β-adrenergic agonist, isoproterenol, was associated with l) enhanced ⁴⁵Ca⁺⁺ efflux and 2) a dependence on the extracellular Na⁺ concentration. Monensin, a sodium ionophore, mimicked the effects of isoproterenol on ⁴⁵Ca⁺⁺ efflux. In the absence of extracellular sodium isoproterenol and monensin failed to significantly release ⁴⁵Ca⁺⁺. Complete inhibition of isoproterenol stimulated amylase release occurred when 75 per cent or greater of the extracellular Na⁺ was replaced by sucrose; carbachol stimulated amylase release was not affected. Tetracaine (0.2 mM to 1.0 mM) inhibited both isoproterenol and carbachol stimulated amylase release and inhibited the ⁴⁵Ca⁺⁺ uptake induced by carbachol. Monensin, a sodium ionophore, mimicked the effects of isoproterenol on amylase release; this effect was significantly reduced in the absence of extracellular Na⁺. It is proposed that a primary step in the release of amylase form mouse parotid gland in response to β-adrenergic stimulation is an increased influx of Na⁺ followed by release of intracellularly stored calcium.     

The form of sodium-calcium competition at the frog myoneural junction

The times required for a steady rate of miniature end-plate potential discharge to be reached in response to changes in extracellular [K⁺], [Na⁺], and [Ca⁺⁺] have been measured. In the presence of 15 mM KCl, Ca⁺⁺ raises and Na⁺ lowers the steady-state mepp frequency; but the depressive effect on Na⁺ is not specific: Li⁺ can replace Na⁺ to a large extent. Mepp frequency has been found to depend on the ratio of [Ca_o ⁺⁺]/[Na_o ⁺]. It is assumed that in the steady state, intracellular sodium will change when extracellular sodium is changed. Because both intracellular and extracellular sodium at motor nerve endings affect acetylcholine release, it is proposed that mepp frequency depends on the ratio [Ca_o] [Na_i]²·/[Na_o]² Two models are proposed. Firstly, to account for the action of sodium and calcium a carrier is postulated for which Ca⁺⁺ and Na⁺ compete. The carrier determines a maximum level of intracellular Ca⁺⁺ far lower than predicted by the Nernst equation for Ca. Secondly, to account for activation of acetylcholine release by a small influx of Ca⁺⁺, the ions are presumed to enter the nerve ending in a two stage process through a small intermediate compartment and to act on the acetylcholine release site in this region rather than after entering directly into the cell.     

Role of external calcium in sodium and chloride transport in the gills of seawater-adaptedMugil capito

Summary When the mulletMugil capito is transferred to medium lacking Ca⁺⁺ (either Ca⁺⁺-free seawater or distilled water) the passive permeability of the gill to Na⁺ and Cl^– is increased and the activating effect of external K⁺ on the Na⁺ and Cl^– effluxes in hyposaline media is inhibited. The permeability of the gill increases progressively in proportion to the time of Ca⁺⁺ deprivation; it declines when Ca⁺⁺ is added again to the external medium. The active mechanisms for ion excretion are not reversible. At external Ca⁺⁺ concentrations from 0.1 to 10 mM the Na⁺ permeability is constant but the activation of Na⁺ efflux by K⁺ shows a maximum at a Ca⁺⁺ concentration of about 1 mM. For activation of Cl^– efflux external bicarbonate must be present, in addition to Ca⁺⁺, suggesting the existence of a Cl^–/HCO ₃ ^– exchange. The mechanism by which Ca⁺⁺ controls the passive branchial permeability is thus probably different from that involved in K⁺ activation of ion excretion. The Ca⁺⁺ effect on the K⁺ sensitive ionic excretory mechanisms seems to be related to intracellular Ca⁺⁺ movements. Thus, on the one hand, substances such as Ruthenium Red and La⁺⁺⁺ which both inhibit Ca⁺⁺ exchange, in media containing Ca⁺⁺ and HCO ₃ ^– also inhibit K⁺ activation of Na⁺ and Cl^– effluxes; on the other hand, the ionophore A 23187, a stimulator of Ca⁺⁺ exchange, when added to these media, activates the Na⁺ and Cl^– effluxes; its maximal effect on the Na⁺ flux occurs at 2 mM Ca⁺⁺.Abbreviations ASW-Ca artificial seawater minus calcium - DW deionised water - DWCa deionised water with 1 mM Ca⁺⁺ added - DWCaHCO ₃ DW with calcium plus bicarbonate - DWHCO ₃ DW with 1 mM sodium bicarbonate added - FW freshwater (tap water) - FWK freshwater with K⁺ added - P. D. potential difference - SW seawater The experiments reported in this paper were done with Jean Maetz who tragically died in August 1977. It is the last report about several years of friendly collaboration     

Calcium dependent action potentials in skeletal muscle fibres of a beetle larva, Xylotrupes dichotomus

The ionic requirement for generating action potentials in ventral longitudinal muscle fibers dissected from beetle larvae was examined by conventional electrophysiological techniques. Muscle fibers that generated only graded responses in physiological saline were able to generate an all-or-none action potential when the potassium permeability of the membrane was inhibited by tetraethylammonium⁺ added to the saline. The peak of the action potential thus elicited was intimately related to the external Ca⁺⁺ concentration. The action potential was blocked by Co⁺⁺ which is known as a competitive inhibitor of Ca-spikes. Neither tetrodotoxin (3 μM) nor a Na-free condition effectively blocked the generation of the action potential. Mg⁺⁺ induced a shift in the peak of the action potential; this was, however, due to the stabilizing action of Mg⁺⁺ but not due to the penetration of Mg⁺⁺ through the muscle membrane. No action potential was elicited in the muscle fiber when immersed in a Ca-free, EGTA saline even when a high concentration of either Mg⁺⁺, Na⁺, or tetraethylammonium⁺ was present. The action potential of the larval muscle fiber was thus concluded to be a Ca-spike, through the channel of which Na⁺ or Mg⁺⁺ did not penetrate.     

Further Studies on the Roles of Sodium and Potassium in the Generation of the Electro-Olfactogram : Effects of mono-, di-, and trivalent cations

In the negative EOG-generating process a cation which can substitute for Na⁺ was sought among the monovalent ions, Li⁺, Rb⁺, Cs⁺, NH₄⁺, and TEA⁺, the divalent ions, Mg⁺⁺, Ca⁺⁺, Sr⁺⁺, Ba⁺⁺, Zn⁺⁺, Cd⁺⁺, Mn⁺⁺, Co⁺⁺, and Ni⁺⁺, and the trivalent ions, Al⁺⁺⁺ and Fe⁺⁺⁺. In Ringer solutions in which Na⁺ was replaced by one of these cations the negative EOG's decreased in amplitude and could not maintain the original amplitudes. In K⁺-Ringer solution in which Na⁺ was replaced by K⁺, the negative EOG's reversed their polarity. Recovery of these reversed potentials was examined in modified Ringer solutions in which Na⁺ was replaced by one of the above cations. Complete recovery was found only in the normal Ringer solution. Thus, it was clarified that Na⁺ plays an irreplaceable role in the generation of the negative EOG's. The sieve hypothesis which was valid for the positive EOG-generating membrane or IPSP was not found applicable in any form to the negative EOG-generating membrane. The reversal of the negative EOG's found in K⁺- , Rb⁺- , and Ba⁺⁺-Ringer solutions was attributed to the exit of the internal K⁺. It is, however, not known whether or not Cl^- permeability increases in these Na⁺-free solutions and contributes to the generation of the reversed EOG's.     

Junctional membrane permeability

Summary Substitution of extracellular Na⁺ by Li⁺ causes depression of junctional membrane permeability inChironomus salivary gland cells; within 3 hr, permeability falls to so low a level that neither fluorescein nor the smaller inorganic ions any longer traverse the junctional membrane in detectable amounts (uncoupling). The effect is Li-specific: if choline⁺ is the Na⁺ substitute, coupling is unchanged. The Li-produced uncoupling is not reversed by restitution of Na⁺. Long-term exposure (>1 hr) of the cells to Ca, Mg-free medium leads also to uncoupling. This uncoupling is fully reversible by early restitution of Ca⁺⁺ or Mg⁺⁺. Coupling is maintained in the presence of either Ca⁺⁺ or Mg⁺⁺, so long as the total divalent concentration is about 12mm. The uncoupling in Ca, Mg-free medium ensues regardless of whether the main monovalent cation is Na, Li or choline.The uncouplings are accompanied by cell depolarization. Repolarization of the cells by inward current causes restoration of coupling; the junctional conductance rises again to its normal level. The effect was shown for Li-produced uncoupling, for uncoupling by prolonged absence of external Ca⁺⁺ and Mg⁺⁺, and for uncoupling produced by dinitrophenol. In all cases, the recoupling has the same features: (1) it develops rapidly upon application of the polarizing current; (2) it is cumulative; (3) it is transient, but outlasts the current; and (4) it appears not to depend on the particular ions carrying the current from the electrodes to the cell. The recoupling is due to repolarization of nonjunctional cell membrane; recoupling can be produced at zero net currernt through the junctional membrane. Recoupling takes place also as a result of chemically produced repolarization; restoration of theK gradients in uncoupled cells causes partial recoupling during the repolarization phase.An explanation of the results on coupling is proposed in terms of known mechanisms of regulation of Ca⁺⁺ flux in cells. The uncouplings are explained by actions raising the Ca⁺⁺ level in the cytoplasmic environment of the junctional membranes; the recoupling is explained by actions lowering this Ca⁺⁺ level.     

Mechanism of the exciting action of noradrenalin and adrenalin on the smooth muscle cells of the portal vein

The ionic mechanism of the exciting action of catecholamines — nonadrenalin and adrenalin — on the muscle cells of the portal vein of the rat was investigated by the method of a double "sucrose bridge." To determine the role of various ions in the action of catecholamines, they were removed from Krebs solution and replaced by other ions. In muscle cells kept in sodium-free Krebs solution, just as under normal conditions, the catecholamines induced depolarization of the membrane, an increase in the spontaneous electrical activity, an increase in the excitability, and a decrease in the amplitude of the electrotonic potentials (ETP), i.e., the resistance of the membrane. The exciting action of catecholamines on muscle cells also did not cease after the removal of Ca⁺⁺ from solution. This action of them was not manifested only in the case when Na⁺ and Ca⁺⁺ were removed simultaneously from the surrounding solution. Thus, the exciting action of noradrenalin and adrenalin on muscle cells of the portal vein is due to a decrease in the permeability of the cell membrane for Na⁺ and Ca⁺⁺ in a definite quantitative ratio.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No. 6, pp. 643–653, November–December, 1970.     

The effects of intracellular iontophoretic injection of calcium and sodium ions on the light response of Limulus ventral photoreceptors

During intracellular iontophoretic injection of Ca⁺⁺ into Limulus ventral photoreceptor cells, there is a progressive diminution of the light response. Following Ca⁺⁺ injection, the size of the light response slowly recovers. Similarly, there is a progressive diminution of the light response during intracellular injection of Na⁺ and recovery after the injection is stopped. The rate of diminution during Na⁺ injection is greater for higher [Ca⁺⁺]_out. In solutions which contain 0.1 mM Ca⁺⁺, there is nearly no progressive decrease in the size of the light response during Na⁺ injection. Intracellular injections of Li⁺ or K⁺ do not progressively decrease the size of the light response. We propose that an increase in [Na⁺]_in leads to an increase in [Ca⁺⁺]_in and that an increase in [Ca⁺⁺]_in by any means leads to a reduction in responsiveness to light.     

Inhibition of Na+-coupled solute transport by calcium in brush border membrane vesicles

Intracellular Ca⁺⁺ is known to influence Na⁺ flux in luminal membranes. Abnormally elevated Ca⁺⁺ levels in some cells is believed to be the primary pathophysiologic defect in cystic fibrosis (CF). This in turn is thought to alter Na⁺ transport which accounts for certain clinical manifestations of this disease. Two Na⁺-dependent intestinal transport mechanisms have been reported to be suppressed or missing in CF. To examine whether alterations in cell Ca⁺⁺ may account for these findings, studies were performed to examine the influence of Ca⁺⁺ on Na⁺-solute co-transport across intestinal luminal membranes. Purified brush border membrane vesicles prepared from rat small bowel were preincubated in either Ca⁺⁺-free buffer or buffer containing 2.5 mM CaCl₂. Ca⁺⁺ loaded vesicles showed marked inhibition of Na⁺ co-transport of taurocholic acid, taurochenodeoxycholic acid, glucose and valine when compared to controls. The uptake of Na⁺ was also significantly reduced by intravesicular Ca⁺⁺. These data demonstrate that intravesicular Ca⁺⁺ inhibits Na⁺-coupled solute transport as well as Na⁺ influx across intestinal brush border membranes. These data suggest that intracellular Ca⁺⁺ may suppress Na⁺-dependent solute absorption in the intestine. Results presented here further support the theory that elevated intracellular Ca⁺⁺ may account for intestinal malabsorption and other altered transport phenomena reported in CF.     

A contribution of an electrogenic Na+ pump to membrane potential in Aplysia neurons

The resting membrane potential (RMP) of Aplysia neurons is very temperature-dependent, and in some cells increases with increasing temperature by as much as 2 mv/°C. RMP at room temperature may significantly exceed the potassium equilibrium potential, which can be determined by measurement of the equilibrium point of the spike after potential. The hyperpolarization on warming is completely abolished by ouabain, replacement of external Na⁺ by Li⁺, removal of external K⁺, and by prolonged exposure to high Ca⁺⁺, while it is independent of external chloride but is increased by cocaine (3 x 10^-3 M). In an identified cell that shows a marked temperature dependence of RMP, both the potassium equilibrium potential and the membrane resistance were found to be relatively independent of temperature. The hyperpolarization on warming, which may increase RMP by as much as 50%, can most reasonably be ascribed to the activity of an electrogenic Na⁺ pump.     

Respiratory pattern generator model using Ca++-induced Ca++ release in neurons shows both pacemaker and reciprocal network properties

There are two contradictory explanations for central respiratory rhythmogenesis. One suggests that respiratory rhythm emerges from interaction between inspiratory and expiratory neural semicenters that inhibit each other and thereby provide reciprocal rhythmic activity (Brown 1914). The other uses bursting pacemaker activity of individual neurons to produce the rhythm (Feldman and Cleland 1982). Hybrid models have been developed to reconcile these two seemingly conflicting mechanisms (Smith et al. 2000; Rybak et al. 2001). Here we report computer simulations that demonstrate a unified mechanism of the two types of oscillator. In the model, we use the interaction of Ca⁺⁺-dependent K⁺ channels (Mifflin et al. 1985) with Ca⁺⁺-induced Ca⁺⁺ release from intracellular stores (McPherson and Campbell 1993), which was recently revealed in neurons (Hernandez-Cruz et al. 1997; Mitra and Slaughter 2002a,b; Scornik et al. 2001). Our computations demonstrate that uncoupled neurons with these intracellular mechanisms show conditional pacemaker properties (Butera et al. 1999) when exposed to steady excitatory inputs. Adding weak inhibitory synapses (based on increased K⁺ conductivity) between two model neural pools surprisingly synchronizes the activity of both neural pools. As inhibitory synaptic connections between the two pools increase from zero to higher values, the model produces first dissociated pacemaker activity of individual neurons, then periodic synchronous bursts of all neurons (inspiratory and expiratory), and finally reciprocal rhythmic activity of the neural pools.     

R 24571: a new powerful inhibitor of red blood cell Ca++-transport ATPase and of calmodulin-regulated functions

Compound R 24571 (1-[bis(p-chlorophenyl)methyl]-3-[2,4-dichloro-β-(2,4-dichlorobenzyloxy)phenethyl]imidazoliniumchloride) is found to be a powerful inhibitor of red blood cell Ca⁺⁺-ATPase as well as Ca⁺⁺ transport into inside-out red blood cell vesicles with an IC₅₀-value of 0.5 and 2 μM, respectively. The inhibitory action of R 24571 is more specific on the calmodulin-dependent fraction of Ca⁺⁺-transport ATPase as compared to the basal Ca⁺⁺-transport ATPase (determined in the absence of calmodulin) and can be antagonized by increasing concentrations of calmodulin in an apparently competitive manner. With respect to other ATPases the action of R 24571 is relatively specific for red blood cell Ca⁺⁺-transport ATPase. Mg⁺⁺-ATPase requires a 40 times higher concentration for halfmaximal inhibition (IC₅₀ = 20 μM) whereas (Na⁺ + K⁺)-transport ATPase is only slightly affected in the investigated concentration range (≤20 μM).     

Effects of Ca ions on action potentials in immature cultured neurons from chick cerebral cortex

Action potentials evoked by depolarizing pulses were studied in immature cultured cerebral cortical neurons from chick embryos. The majority of action potentials were rather small, and they were still elicited in the presence of 10^?7 gm/ml tetrodotoxin (TTX), but were almost completely abolished in Na⁺-free solution or by 10^?5 gm/ml TTX in Tyrode's solution. The elevation of external Ca²⁺ concentration not only increased the maximum rates of rise of action potentials in normal Tyrode's solution with and without low (10^?7 gm/ml) TTX but also regenerated action potentials in high (10^?5 gm/ml) TTX-containing Tyrode's solution or in Na⁺-free solution. These high Ca²⁺ effects were blocked by Mn²⁺ or Co²⁺. These results suggest that action potentials, which were predominantly Na-dependent, are partially contributed by Ca ions in immature chick cerebral cortical neurons.     

Multiple modes of a conditional neural oscillator

We present a model for a conditional bursting neuron consisting of five conductances: Hodgkin-Huxley type time- and voltage-dependent Na⁺ and K⁺ conductances, a calcium activated voltage-dependent K⁺ conductance, a calcium-inhibited time- and voltage-dependent Ca⁺⁺ conductance, and a leakage Cl(_– conductance. With an initial set of parameters (versionS), the model shows a hyperpolarized steady-state membrane potential at which the neuron is silent. Increasingg _Na and decreasingg _Cl, whereg _i , is the maximal conductance for speciesi, produces bursts of action potentials (BursterN). Alternatively, an increase ing _Ca produces a different bursting state (BursterC). The two bursting states differ in the periods and amplitudes of their bursting pacemaker potentials. They show different steady-stateI–V curves under simulated voltage-clamp conditions; in simulations that mimic a steady-stateI–V curve taken under experimental conditions only BursterN shows a negative slope resistance region. ModelC continues to burst in the presence of TTX, while bursting in ModelN is suppressed in TTX. Hybrid models show a smooth transition between the two states.