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AJ96
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Literature
38 records
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in hippocampal CA3 pyramidal neurons
high-voltage-activated (HVA) calcium currents. We characterized the LVA
current by recording whole-cell Ca2+ currents from acutely isolated rat
hippocampal CA3 pyramidal neurons in 2 mM Ca2+. Long depolarizing steps to -50
mV revealed two components to the LVA current: transient and sustained. The
transient phase had a fast decay time constant of 59 msec. The sustained phase
persisted throughout the depolarization, even for steps lasting several
seconds. The transient current was inhibited by the classic T-type channel
antagonists Ni2+ and amiloride. The anticonvulsant phenytoin preferentially
blocked the sustained phase, but ethosuximide had no effect. Steady-state
inactivation of the transient component was half-maximal at -80 mV.
Nimodipine, an L-type channel antagonist, partly inhibited the sustained
current. BayK-8644, an L-type channel agonist, potentiated the sustained
current. Calciseptine, another L-type channel antagonist, inhibited the
sustained component. omega-Conotoxin-MVIIC, a nonselective toxin for HVA
channels, had no effect on either of the LVA current components.
omega-Grammotoxin-SIA, another nonselective toxin, partially inhibited the
sustained component. The voltage dependence of activation of the
nimodipine-sensitive current could be fit with a single Boltzmann, consistent
with a homogenous population of L-type channels in CA3 neurons. Half-maximal
activation of the nimodipine-sensitive current occurred at -30 mV,
considerably more negative than the remaining HVA current. These results
suggest that in physiologic Ca2+ more than one type of Ca2+ channel
contributes to the LVA current in CA3 neurons. The transient current is
carried by T-type channels. The sustained current is carried, at least in
part, by dihydropyridine-sensitive channels. Thus, the designation
"low-voltage-activated" should not be limited to T-type channels.
These findings challenge the traditional designation of L-type channels as
exclusively HVA and reveal a possible role in subthreshold Ca2+ signaling.
