scholarly journals Subthreshold membrane potential oscillations in inferior olive neurons are dynamically regulated by P/Q- and T-type calcium channels: a study in mutant mice

2010 ◽  
Vol 588 (16) ◽  
pp. 3031-3043 ◽  
Author(s):  
Soonwook Choi ◽  
Eunah Yu ◽  
Daesoo Kim ◽  
Francisco J. Urbano ◽  
Vladimir Makarenko ◽  
...  
2014 ◽  
Vol 112 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Di Wang ◽  
Sten Grillner ◽  
Peter Wallén

The lamprey central nervous system has been used extensively as a model system for investigating the networks underlying vertebrate motor behavior. The locomotor networks can be activated by application of glutamate agonists, such as N-methyl-D-aspartic acid (NMDA), to the isolated spinal cord preparation. Many spinal neurons are capable of generating pacemaker-like membrane potential oscillations upon activation of NMDA receptors. These oscillations rely on the voltage-dependent properties of NMDA receptors in interaction with voltage-dependent potassium and calcium-dependent potassium (KCa) channels, as well as low voltage-activated calcium channels. Upon membrane depolarization, influx of calcium will activate KCa channels, which in turn, will contribute to repolarization and termination of the depolarized phase. The appearance of the NMDA-induced oscillations varies markedly between spinal cord preparations; they may either have a pronounced, depolarized plateau phase or be characterized by a short-lasting depolarization lasting approximately 200–300 ms without a plateau. Both types of oscillations increase in frequency with increased concentrations of NMDA. Here, we characterize these two types of membrane potential oscillations and show that they depend on the level of endogenous release of 5-HT in the spinal cord preparations. In the lamprey, 5-HT acts to block voltage-dependent calcium channels and will thereby modulate the activity of KCa channels. When 5-HT antagonists were administered, the plateau-like oscillations were converted to the second type of oscillations lacking a plateau phase. Conversely, plateau-like oscillations can be induced or prolonged by 5-HT agonists. These properties are most likely of significance for the modulatory action of 5-HT on the spinal networks for locomotion.


1999 ◽  
Vol 81 (3) ◽  
pp. 1318-1329 ◽  
Author(s):  
Jesper Tegnér ◽  
Sten Grillner

Interactive effects of the GABABergic modulation of calcium channels and calcium-dependent potassium channels in lamprey. The GABAB-mediated modulation of spinal neurons in the lamprey is investigated in this study. Activation of GABAB receptors reduces calcium currents through both low- (LVA) and high-voltage activated (HVA) calcium channels, which subsequently results in the reduction of the calcium-dependent potassium (KCa) current. This in turn will reduce the peak amplitude of the afterhyperpolarization (AHP). We used the modulatory effects of GABAB receptor activation on N-methyl-d-aspartate (NMDA)-induced, TTX-resistant membrane potential oscillations as an experimental model in which to separate the effects of GABAB receptor activation on LVA calcium channels from that on KCachannels. We show experimentally and by using simulations that a direct effect on LVA calcium channels can account for the effects of GABAB receptor activation on intrinsic membrane potential oscillations to a larger extent than indirect effects mediated via KCa channels. Furthermore, by conducting experiments and simulations on intrinsic membrane potential oscillations, we find that KCa channels may be activated by calcium entering through LVA calcium channels, providing that the decay kinetics of the calcium that enters through LVA calcium channels is not as slow as the calcium entering via NMDA receptors. A combined experimental and computational analysis revealed that the LVA calcium current also contributes to neuronal firing properties.


1997 ◽  
Vol 63 (2-3) ◽  
pp. 221-239 ◽  
Author(s):  
Marko Marhl ◽  
Stefan Schuster ◽  
Milan Brumen ◽  
Reinhart Heinrich

1993 ◽  
Vol 70 (1) ◽  
pp. 144-157 ◽  
Author(s):  
R. Klink ◽  
A. Alonso

1. Layer II of the medial entorhinal cortex is composed of two electrophysiologically and morphologically distinct types of projection neurons: stellate cells (SCs), which are distinguished by rhythmic subthreshold oscillatory activity, and non-SCs. The ionic mechanisms underlying their differential electroresponsiveness, particularly in the subthreshold range of membrane potentials, were investigated in an "in vitro" slice preparation. 2. In both SCs and non-SCs, the apparent membrane input resistance was markedly voltage dependent, respectively decreasing or increasing at hyperpolarized or subthreshold depolarized potential levels. Thus the neurons displayed inward rectification in the hyperpolarizing and depolarizing range. 3. In the depolarizing range, inward rectification was blocked by tetrodotoxin (TTX, 1 microM) in both types of neurons and thus shown to depend on the presence of a persistent low-threshold Na+ conductance (gNap). However, in the presence of TTX, pronounced outward rectification became manifest in the subthreshold depolarizing range of membrane potentials (positive to -60 mV) in the SCs but not in the non-SCs. 4. The rhythmic subthreshold membrane potential oscillations that were present only in the SCs were abolished by TTX and not by Ca2+ conductance block with Cd2+ or Co2+. Subthreshold oscillations thus rely on the activation of voltage-gated Na+, and not Ca2+, conductances. The Ca2+ conductance block also had no effect on the subthreshold outward rectification. 5. Prominent time-dependent inward rectification in the hyperpolarizing range in the SCs persisted after Na(+)- and Ca2+ conductance block. This rectification was not affected by Ba2+ (1 mM), but was blocked by Cs+ (1-4 mM). Therefore, it is most probably generated by a hyperpolarization-activated cationic current (Q-like current). However, the Q-like current appears to play no major role in the generation of subthreshold rhythmic membrane potential oscillations, because these persisted in the presence of Cs+. 6. On the other hand, in the SCs, the fast, sustained, outward rectification that strongly developed (after Na+ conductance block) at the oscillatory voltage level was not affected by Cs+ but was blocked by Ba2+ (1 mM). Barium was also effective in blocking the subthreshold membrane potential oscillations. 7. In the non-SCs, which do not generate subthreshold rhythmic membrane potential oscillations or manifest subthreshold outward rectification in TTX, Ca2+ conductance block abolished spike repolarization and caused the development of long-lasting Na(+)-dependent plateau potentials at a high suprathreshold voltage level. At this level, where prominent delayed rectification is present, the Na+ plateaus sustained rhythmic membrane potential oscillations.(ABSTRACT TRUNCATED AT 400 WORDS)


1999 ◽  
Vol 81 (3) ◽  
pp. 1296-1307 ◽  
Author(s):  
C. Andrew Chapman ◽  
Jean-Claude Lacaille

Intrinsic theta-frequency membrane potential oscillations in hippocampal CA1 interneurons of stratum lacunosum-moleculare. The ionic conductances underlying membrane potential oscillations of hippocampal CA1 interneurons located near the border between stratum lacunosum-moleculare and stratum radiatum (LM) were investigated using whole cell current-clamp recordings in rat hippocampal slices. At 22°C, when LM cells were depolarized near spike threshold by current injection, 91% of cells displayed 2–5 Hz oscillations in membrane potential, which caused rhythmic firing. At 32°C, mean oscillation frequency increased to 7.1 Hz. Oscillations were voltage dependent and were eliminated by hyperpolarizing cells 6–10 mV below spike threshold. Blockade of ionotropic glutamate and GABA synaptic transmission did not affect oscillations, indicating that they were not synaptically driven. Oscillations were eliminated by tetrodotoxin, suggesting that Na+ currents generate the depolarizing phase of oscillations. Oscillations were not affected by blocking Ca2+ currents with Cd2+ or Ca2+-free ACSF or by blocking the hyperpolarization-activated current ( I h) with Cs+. Both Ba2+ and a low concentration of 4-aminopyridine (4-AP) reduced oscillations but TEA did not. Theta-frequency oscillations were much less common in interneurons located in stratum oriens. Intrinsic membrane potential oscillations in LM cells of the CA1 region thus involve an interplay between inward Na+ currents and outward K+ currents sensitive to Ba2+ and 4-AP. These oscillations may participate in rhythmic inhibition and synchronization of pyramidal neurons during theta activity in vivo.


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