Serotonin differentially modulates the electrical properties of different subsets of taste receptor cells in bullfrog

Serotonin (5-hydroxytryptamin, 5-HT) is localized in taste bud cells of vertebrates. Effects of the external application of 5-HT on the membrane currents of frog taste receptor cells (TRCs) were investigated using patch-clamp technique in whole-cell configuration. The 5-HT (0.1-1 micro m) and 5-HT1A receptor agonist (+/-)-8-OH-2-(D1-n-propyl-amino)tetralin (8-OH-DPAT) (1-20 micro m) inhibited both voltage-gated sodium current (INa) and voltage-gated potassium current (IK) in 50% of TRCs, but potentiated IK without any significant effect on INa in another subset of 18% of TRCs. Voltage-gated currents in the residual TRCs were not affected by 5-HT or 8-OH-DPAT. External application of 10 micro m forskolin and 300 micro m 8-cpt cAMP [8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate] mimicked the inhibitory effect of 5-HT and 8-OH-DPAT on IK and INa while internal dialysis with 50 micro m protein kinase A inhibitor prevented the 5-HT-mediated inhibitory effects on IK and INa in TRCs. Internal dialysis of TRCs with high Ca2+-pipette solution (1 micro m) increased the IK in 58% of TRCs. The 5-HT reversibly increased the [Ca2+]i in 17% of TRCs when measured by Ca2+-imaging using a Ca2+-sensitive dye (fura-2 AM). These results suggest that 5-HT differentially modulates the voltage-gated membrane currents in different subsets of TRCs.     

Stimulus-dependent blockade of node of Ranvier sodium channels by ethmozine

The effect of antiarrhythmic drug ethmozine on sodium channels in Ranvier node was studied by the voltage clamp technique. Both outside and inside application of ethmozine induced a decrease of sodium current I Na, the time course of I Na and the sodium inactivation being unchanged. The ethmozine-induced Na channel blockade induced tonic (stationary) and phasic (transient stimulus-dependent) components. The tonic blockade of I Na developed slowly and could be accelerated by frequent electric stimulation of the membrane. The phase dependent blockade became more profound with an increase in the pulse rate or amplitude of depolarizing pulses. The prolonged (1 s) membrane depolarization did not bring about an additional blockade of I Na. It is concluded that the phasic blockade is due to the interaction of ethmozine with open Na channels. The noninactivating batrachotoxin-modified Na channels were insensitive to ethmozine. It is found that the increase in outside potassium concentration from 2.5 to 20mM induced both a decrease of the tonic blockade and an increase of the phasic one. The possible nature of the ionic blockade is discussed. The effect of ethmozine is compared with that of tertiary and quaternary local anesthetics.     

Changes in ion channel expression accompany cell cycle progression of spinal cord astrocytes

Arrest of spinal cord astrocytes at defined stages of the cell cycle clock causes significant changes in the expression of voltage-activated Na(+) and K(+) currents. Arrest of actively proliferating astrocytes in G1/G0 by all-trans-retinoic acid induces premature expression of inwardly rectifying K(+) currents (IK(IR)) typically expressed only in differentiated astrocytes. By contrast, arrest in S phase by ara-C or Aphidicolin leads to a greater than twofold increase in "delayed" outwardly rectifying currents (IK(D)) and a concomitant decrease in IK(IR). Pharmacological blockade of IK(D) by TEA and 4AP caused proliferating astrocytes to arrest in G0/G1, suggesting that activity of these channels is required for G1/S checkpoint progression. Conversely, in quiescent astrocytes, inhibition of IK(IR) by 30 microM BaCl(2) led to an increase in astrocyte proliferation and to an increase in the number of cells in S phase from 5% to 26%. These data suggest that a downregulation of K(IR) promotes cell cycle progression through the G1/S checkpoint. Blockade of IK(IR) in actively proliferating cells, however, leads to an accumulation in G2/M, suggesting that reappearance of this current may be critical for progression beyond DNA synthesis. Interestingly, Na(+) currents (INa(+)) are increased greater than fourfold in S phase-arrested cells, yet their pharmacological blockade by TTX has no effect on cell cycle progression. However, the resting membrane potential of S phase-arrested cells increases profoundly, and manipulation of membrane potential by the application of low concentrations of ouabain, or reduction of extracellular potassium, induces the accumulation of quiescent astrocytes in S phase of the cell cycle, suggesting that either depolarization or intracellular sodium, or both, play an important role in promoting astrocyte proliferation.     

Flurazepam interaction with sodium and potassium channels in squid giant axon

External application of 0.05-1.0 mM flurazepam was found to partially block both sodium and potassium currents in voltage-clamped squid giant axons. At the same concentration the fractional block of the potassium current was found to be 3 times greater than that of the sodium current. In the presence of the drug the potassium current appeared to "inactivate', as flurazepam block became more profound during the course of the depolarization. The decay of the potassium current can be explained by a model in which flurazepam enters and blocks the potassium channels only after they have opened. Once bound in the potassium channel, removal of flurazepam from its binding site develops slowly (tau = 48 ms). Thus repetitive stimulation of the nerve produced a cumulative block. When applied inside the axon flurazepam was found to be 1.5 (n = 4) times more potent blocker of potassium channels than following external application. This result suggests that when applied externally, a neutral form of the drug diffuses across the membrane and blocks occurs from the inner end of the channel.     

Apolipoprotein E4 suppresses delayed-rectifier potassium channels in membrane patches excised from hippocampal neurons

Recent studies show a clear association between Alzheimer's disease (AD) and the apolipoprotein E epsilon 4 allele (APOE4). The mechanisms underlying apoE4-mediated detrimental effects have not been well-clarified. The present study investigates possible effects of apoE4 on the delayed-rectifier potassium (IK) channels in inside-out membrane patches excised from rat hippocampal neurons. Acute application of apoE4 (0.5 microM) to the inside of the membrane patches markedly and reversibly suppressed the single IK channel activities. The average open probability and open frequency of IK channels decreased by (92.6+/-7.1)% and (88.6+/-3.2)%, respectively. The mean open time of IK channels decreased by (81.6+/-6.7)%, and the mean closed-time of them increased by 6.9+/-1.9 fold. Meanwhile, the mean current amplitude of IK channels was not significantly affected. In contrast, application of apolipoprotein A (apoA, 0.5 microM), another member of apolipoprotein family with similar molecular weight and amino acid sequence to apoE4, did not exhibit any effects on IK currents. These results indicate that apoE4 molecules can rapidly suppress the activities of IK channels in hippocampal neurons when they act on the inner side of the neuronal membrane. We propose that the overproduction of apoE4 in neurons may suppress normal IK channel activities and thus be responsible for the late-developed neuronal damages related to the pathogenesis of AD.     

Physiology of morphologically identified cells of the bullfrog fungiform papilla

Voltage-gated ionic current and the response to quinine were studied on the four types of morphologically identified taste cells of the bullfrog fungiform papilla by whole-cell patch clamp recording with a Lucifer yellow-filled pipette. Dye-coupled type Ia cells (mucous cells) did not show voltage-activated currents. Type Ib cells (wing cells) characterized by the fin-like processes, type II cells (rod cells) having a thick straight dendrite running to the surface and type III cells with a thin dendrite had voltage-gated sodium (INa) and potassium currents (IK) and generated action potentials. The amplitude of INa was significantly larger in type Ib and II cells than in type III cells. Type Ib and II cells responded to quinine but Type III cells did not.     

钙离子电导及在视网膜神经节细胞放电行为中的作用

Fohlmeister-Coleman-Miller model of retinal ganglion cells consists of five ion channels;these are sodium channels,calcium channels,and 3 types of potassium channels.An increasing number of studies have investigated sodium channels,voltage-gated potassium channels,and delayed rectifier potassium channels.However,little is known about calcium channels,and in particular the dynamics and computational models of calcium ions.Retinal prostheses have been designed to assist with sight recovery for the blind,and in the present study,the effects of calcium ions in retinal ganglion cell models were analyzed with regard to calcium channel potential and calcium-activated potassium potential.Using MATLAB software,calcium conductance and calcium current from the Fohlmeister-Coleman-Miller model,under clamped voltages,were numerically computed using backward Euler methods.Subsequently,the Fohlmeister-Coleman-Miller model was simulated with the absence of calcium-current(ICa) or calcium-activated potassium current(IK,Ca).The model was also analyzed according to the phase plane method.The relationship curve between peak calcium current and clamped potentials revealed an inverted bell shape,and the calcium-activated potassium current increased the frequency of firing and the peak of membrane potential.Results suggested that calcium ion concentrations play an important role in controlling the peak and the magnitude of peak membrane voltage in retinal ganglion cells.     

Differential effects of pentylenetetrazole on ion currents of Aplysia neurones

The effect of the convulsant drug pentylenetetrazole (PTZ) on separated membrane current components has been studied in identified voltage-clamped Aplysia neurones. External PTZ blocks the voltage-dependent Na+, Ca2+ currents and the delayed rectifier current (INa, ICa and IK,V, respectively). The amplitude of the Ca2+-activated K+ current (IK,Ca) is increased. The amplitude of the fast inactivating K+ current (IA) is transiently increased at low concentrations of PTZ but is depressed at higher concentrations or after long-lasting application of the drug. The effect of PTZ on leakage current (IL) seems to depend on the cell type. In some cells (R-15, L-7, LP-1) IL is decreased while it is increased in other cells (L-11, BL-1, BR-1). PTZ accelerates the inactivation of IK,V and IA and shifts the current-voltage relation of ICa to negative voltages by 5-8 mV. Pressure injection of PTZ into the neurone did not affect IK,V or IK,Ca. Thus PTZ seems to act on the outside of the plasma membrane. The effect of external PTZ on INa, ICa, IK,V and IL is also observed if the internal Ca2+ activity is buffered with EGTA suggesting that an increase in the internal Ca2+ activity is not involved. At -40 mV PTZ induces a tetrodotoxin-insensitive inward current carried by Na+ ions. PTZ transforms the beating pacemaker cell L-11 into a bursting pacemaker and the bursting pacemaker cell R-15 exhibits 'square-wave'-like oscillations of the membrane potential.     

Cisplatin modulates voltage gated channel currents of dorsal root ganglion neurons of rats

The anticancer drug cis-diammindichloroplatin (CDDP, cisplatin) causes severe side effects like peripheral sensitive neuropathy. The toxicity of CDDP has been linked to changes in intracellular calcium homeostasis ([Ca2+]i). Voltage activated calcium channel currents (ICa(V)) are important for the regulation of [Ca2+]i; therefore, this study was designed to examine the effect of CDDP on ICa(V) in comparison to voltage activated potassium (IK(V)) and sodium (INa(V)) channel currents using the whole cell patch clamp method on dorsal root ganglion neurons of rats. In small neurons (or=?25 microm) were less sensitive to CDDP. The peak ICa(V) was reduced by 14.1+/-2.3% and IK(V) by 12.8+/-3.4% (100 microM). The sensitivity of INa(V) in large neurons to CDDP was not different compared to small neurons. We conclude that the reduction of ICa(V) in small cells may be responsible for the neurotoxic side effects CDDP causes in sensory neurons.     

Properties and rundown of sodium-activated potassium channels in rat olfactory bulb neurons.

We have used single-channel recording techniques to investigate the properties of sodium-activated potassium channels (KNa channels) in cultured rat olfactory bulb neurons, and in large neurons in the mitral cell layer of thin slices of olfactory bulb. Ion channels highly selective for potassium over sodium and chloride, and requiring 10-180 mM internal sodium (Nai) for their activation, were present in approximately 75% of inside-out membrane patches detached from cultured olfactory bulb neurons. Most of these patches contained several KNa channels. KNa channels were seen in cell-attached patches only when Nai was raised by including veratridine in the extracellular medium. Preincubation of the cell in TTX or removal of extracellular sodium prevented this effect of veratridine, confirming that the channels observed under these conditions were indeed KNa channels. Lithium did not substitute for Nai in activating these channels. With 150 mM potassium on both sides of the membrane, KNa channels had a single-channel conductance of 172 pS, and at least two subconducting states were observed in addition to this fully open state. Under these ionic conditions, the channels exhibited linear fully open channel current-voltage curves over the potential range of -100 to 0 mV. At voltages more positive than the potassium equilibrium potential, the single-channel currents exhibited inward rectification as a result of sodium block of outward potassium current. The channels opened in bursts, during which they fluctuated between the fully open and closed states, and the substates. Between bursts they sometimes entered a long-lived inactive state that could last for up to several minutes. In addition, KNa channels in the detached patches exhibited rundown, a progressive irreversible loss in activity, over a time course that varied from less than 1 min to longer than 1 hr. Rundown of KNa channel activity in cell-attached patches (in the presence of veratridine) did not occur, suggesting that some intracellular factor necessary for KNa channel activity is lost when the membrane patch is detached from the cell.     

Caffeine modulates potassium currents in Drosophila neurons

We investigated the effects of caffeine on the delayed-rectifier potassium current (IK(DR)) which is important in repolarizing the membrane potential, and the transient A-type potassium current (IK(A)) which regulates neuronal firing threshold and the rate of repetitive action potentials. The whole-cell patch-clamp technique was used to measure the currents from cultured Drosophila neurons derived from embryonic neuroblasts. The currents were measured from neurons before and after the application of 1mM caffeine to the external saline of the same neuron. IK(DR) measured in the caffeine-containing solution (470+/-36 pA, n=18), was smaller than that measured in the control 6K/0Ca Tris solution (745+/-51 pA, n=18). IK(A) measured in the caffeine-containing solution (17+/-2 pA, n=16) was smaller than that measured in the control 6K/0Ca Tris solution (35+/-4 pA, n=16). These results indicate that caffeine reduces IK(DR) and IK(A) amplitudes and possibly leads to increased action potential frequency and enhanced neuronal excitability.     

Blockade of U50488H on potassium currents of acutely isolated mouse hippocampal CA3 pyramidal neurons

The actions of the opioid agonist U50488H on IA and IK were examined in acutely isolated mouse hippocampal CA3 pyramidal neurons using the whole-cell patch clamp technique. U50488H caused a concentration dependent, rapidly developing and reversible inhibition of voltage-activated IA and IK. The inhibitory actions were still observed in the presence of 30 microM naloxone or 5 microM nor-binaltorphimine dihydrochloride. The IC50 values for the blockade of IA and IK were calculated as 20.1.9 and 3.7 microM, respectively. In the presence of 3.3 microM U50488H, repetitive stimulation induced use-dependent inhibition of IA and IK. A 10 microM concentration of U50488H positively shifted the half-activation membrane potential of IA by +11 mV, but negatively shifted IK by -14 mV. These results demonstrate that U50488H can directly inhibit neuronal IA and IK without involvement of the activation of kappa-opioid receptors.     

Characterization of mRNA responsible for induction of functional sodium channels in Xenopus oocytes

When Xenopus laevis oocytes were microinjected with poly(A)+ mRNA isolated from adult rat brains or electric organs of Electrophorus electricus, the oocytes developed functional sodium channels. Upon application of veratrine, the microinjected oocytes exhibited transient depolarization, resulting in spontaneous repetitive spikes in some occasions, and action potentials. These responses were mediated mainly by external Na ions, prolonged by scorpion toxin, completely blocked by tetrodotoxin, and suppressed by local anesthetics. Thus the mRNA-induced sodium channels exhibited essentially all the functional properties expected for native sodium channels in nerve and muscle membranes. Rat brain mRNA was fractionated into 4 fractions by sucrose gradient centrifugation. Each fraction and various combinations of them were examined for the efficiency in inducing functional sodium channels in Xenopus oocytes. A fraction corresponding to mRNA of approximately 30S to 46S was found to contain all mRNA necessary for the expression of the channels, indicating that mRNA of smaller sizes expected to code for smaller polypeptides may not be required.     

Effects of drugs interfering with sodium channels and calcium channels on the release of endogenous dopamine from superfused substantia nigra slices

The importance of voltage-dependent sodium channels and different types of voltage-sensitive calcium channels for depolarisation-induced release of endogenous dopamine from dendrites and cell bodies in superfused guinea pig substantia nigra slices was investigated. The stimulatory effect of veratridine (10 μM) on dopamine release was only marginally attenuated in Ca²⁺-free medium but was completely blocked by tetrodotoxin (1 μM) and by the dopamine reuptake inhibitor GBR 12909 (10 μM). Low extracellular concentration of Na⁺ stimulated the dopamine release. Potassium-evoked dopamine release was completely Ca²⁺-dependent, not blocked by GBR 12909 and partially blocked by tetrodotoxin. Nifedipine (20 μM), ω-conotoxin GVIA (0.5 μM), penfluridol (5 μM), and Ni²⁺ (20 μM) had no effect, amiloride (1 mM) attenuated and neomycin (350 μM), and ω-agatoxin IVA (1 μM) almost totally blocked the potassium-induced dopamine release. The results suggest that veratridine released dopamine mostly by reversing the dopamine transporter. High concentrations of potassium induced release of nigral dopamine by opening of voltage-sensitive calcium channels of P/Q type but not L-type, N-type and probably not T-type. The depolarisation evoked by high concentrations of potassium seems to open voltage-sensitive calcium channels both by the depolarisation induced by potassium per se and by the secondary depolarisation induced by opening of voltage-dependent sodium channels. Synapse 26:359–369, 1997. © 1997 Wiley-Liss Inc.     

Scorpion toxin prolongs an inactivation phase of the voltage-dependent sodium current in rat isolated single hippocampal neurons

The effects of scorpion toxin on the voltage-dependent sodium current (INa) of CA1 pyramidal neurons isolated from rat hippocampus were studied under the single-electrode voltage-clamp condition using a 'concentration-clamp' technique. The toxin increased the peak amplitude of INa and prolonged its inactivation phase in a time- and dose-dependent manner. Inactivation phase of INa proceeded with two exponential components in the absence (control) and presence of the toxin. In the toxin-treated neurons, both the time constant of slow component and its fractional contribution to the total current increased dose-dependently while the fractional contribution of the fast one decreased in a dose-dependent fashion without changing its time constant. Actions of scorpion toxin on the sodium channels of hippocampal pyramidal neurons were essentially similar to those of peripheral preparations. Therefore, it can be concluded that the sodium channels of mammalian brain neurons have structures and functions similar to peripheral channels.     

Voltage clamp analysis of membrane currents in larval muscle fibers of Drosophila: alteration of potassium currents in Shaker mutants

The body wall muscles in Drosophila larvae are suitable for voltage clamp analysis of changes in membrane excitability caused by mutations. Both inward and outward ionic currents are present in these muscle fibers. The inward current is mediated by voltage-dependent Ca2+ channels. In Ca2+-free saline, the inward current is eliminated. The remaining outward K+ currents consist of two distinct components, an early transient IA and a delayed steady IK, which are separable by differences in the rate and voltage dependence of activation and inactivation. The steady-state and kinetic properties of the activation and inactivation processes of these two currents are analyzed. The results provide a basis for quantitative analysis of altered membrane currents in behavioral mutants of Drosophila. Previous studies indicate that mutations in the Shaker (Sh) locus alter excitability in both nerve and muscle in Drosophila. Our results support the idea that the channels mediating IA are molecularly distinct from those mediating IK. All Sh mutations studied specifically affect IA without changing the properties of the calcium current and IK. In certain alleles (ShKS133, Sh102, and ShM) IA is eliminated, permitting detailed studies of IK in isolation of IA. Studies of the alleles that do not eliminate IA provide additional information of the channels. In one such allele, Sh5, voltage dependence of IA activation is shifted to more positive potentials. This is accompanied by a less pronounced shift in the voltage dependence of inactivation. These results suggest that Sh5 mutation affects the voltage-sensitive mechanism of both activation and inactivation processes and that these two processes are not controlled by independent parts of the channel. Furthermore, the differential effects of these alleles on different excitable membranes imply that other genes take part in the control of IA. The effects of Sh5 on muscle depend on developmental stage. In larval muscle, Sh5 reduces the amplitude of IA because of the shift in the current-voltage (I-V) relation. In contrast, in adult Sh5 muscles, IA is reported to be normal in amplitude but shows abnormally rapid inactivation (Salkoff, L., and R. Wyman (1981) Nature 293: 228-230). A different allele, ShrK0120, causes a clear defect in nerve excitability, but analysis of IA in ShrK0120 larval muscle reveals I-V relations, inactivation, and recovery from inactivation similar to those seen in normal fibers. We suggest a possible mechanism of combinations of multiple interacting genes participating in the control of potassium channels to account for the presence of a variety of potassium channels in different excitable membranes.     

Lidocaine selectively blocks abnormal impulses arising from noninactivating Na channels

Abnormal, repetitive impulse firing arising from incomplete inactivation of Na+ channels may be involved in several diseases of muscle and nerve, including familial myotonias and neuropathic pain syndromes. Systemic local anesthetics have been shown to have clinical efficacy against myotonias and some forms of neuropathic pain, so we sought to develop an in vitro model to examine the cellular basis for these drugs' effects. In frog sciatic nerves, studied in vitro by the sucrose-gap method, peptide alpha-toxins from sea anemone (ATXII) or scorpion (LQIIa) venom, which inhibit Na+ channel inactivation, induced repetitively firing compound action potentials (CAPs) superimposed on a plateau depolarization lasting several seconds. The initial spike of the CAP was unaffected, but the plateau and repetitive firing were strongly suppressed by 5-30 microM lidocaine. Lidocaine caused a rapid, concentration-dependent decay of the plateau, quantitatively consistent with blockade of open Na(+) channels. Early and late repetitive firing were equally suppressed by lidocaine with IC50 = 10 microM. After washout of lidocaine and LQIIa, the plateau and repetitive firing remained for > 1 h, showing that lidocaine had not caused dissociation of channel-bound alpha-toxin. These findings indicate that therapeutic concentrations of lidocaine can reverse the "abnormal" features of action potentials caused by non-inactivating Na+ channels without affecting the normal spike component.     

An unusually small potassium current that is well-suited to a retinal neuron which is chronically depolarized

Here we describe a sustained outward potassium current (IK) in retinal horizontal cells (HCs). IK is unusually small over the range of membrane potentials normally experienced by these cells, which are chronically depolarized. We hypothesize that this unique IK will reduce the amount of neurotransmitter required to shift the cell's membrane potential over a wide range, and will minimize the redistribution of potassium ions across the post-synaptic membrane when the cell is depolarized.     

The postsynaptic effects of substance P in the frog neuromuscular synapse]

The effect of substance P on the end-plate currents (EPC) and miniature EPC (MEPC) was studied in the "cut" sartorius muscle of the frog using voltage-clamp technique after acetylcholinesterase inhibition. Substance P in the concentration 5.10(-7)-1.10(-6) mol/l had no effect on the amplitude and time course of the single EPC and MEPC, but promoted significant prolongation of EPC decay during repetitive nerve stimulation (10/s), which indicated development of postsynaptic potentiation. Elevation of the substance P concentration to 5.10(-6) mol/l has led to the shortening of single EPS decay and more significant depression of the EPC amplitude in trains. This effect was connected with a decrease of the postsynaptic membrane sensitivity to acetylcholine, i. e. development of desensitization.     

Interaction between repetitive stimulation of the sciatic nerve and functional ablation of cerebellar nucleus interpositus in the rat

It is established that cerebellar nuclei exert a significant effect on the excitability of spinal neurons. However, their output is heterogeneous. Conditioning trains of dentate nucleus stimuli are known to modify the post-synaptic potentials evoked in motoneurons by stimulation of group Ia and Ib afferents in appropriate peripheral nerves. The role of the interpositus nucleus in the modulation of the excitability of rat spinal cord remains unclear. We investigated the interactions between tetrodotoxin (TTX)-induced inactivation of the interpositus cerebellar nuclei and repetitive electrical stimulation of the ipsilateral sciatic nerve (proximal segment) in the anesthetized rat. TTX (10 microM) was administered in cerebellar nuclei by the technique of microdialysis (coordinates of the extremity of the guide related to bregma: AP: -11.6, L: +2.3, V: -4.6). Peripheral stimulation consisted of trains of electric stimuli at a rate of 10 Hz, which were repeated every second during 1 hour. Stimulus intensity was adjusted to produce constant somatosensory evoked potentials. H-reflex, F-wave and M responses of the plantaris muscles were analysed ipsilaterally. H-reflex recruitment curve, Hmax/Mmax ratios, F-wave persistence and mean F/mean M ratios were studied. Functional blockade of cerebellar interpositus nucleus reduced the slope of H-reflex recruitment curve without affecting the Hmax/Mmax ratio, and depressed both F-waves persistence and mean F/mean M ratios. Concomitant repetitive stimulation of the sciatic nerve counteracted the depression of the H-reflex recruitment curve, without interacting with F-waves depression. Our results (1) show that TTX-sensitive sodium channels in cerebellar nucleus interpositus modulate the H-reflex recruitment, and (2) reveal an interaction between TTX-sensitive sodium channels in cerebellar nuclei and afferent repetitive activity not described so far.