N- and L-type calcium channel involvement in depolarization-induced suppression of inhibition in rat hippocampal CA1 cells

摘要

class="enumerated" style="list-style-type:decimal">We investigated depolarization-induced suppression of inhibition (DSI) under whole-cell voltage clamp in CA1 pyramidal neurons of rat hippocampal slices. DSI, a transient reduction in monosynaptic evoked GABAAergic IPSCs lasting for ∼1 min, was induced by depolarizing the pyramidal cell to −10 or 0 mV for 1 or 2 s.Raising extracellular Ca²⁺ concentration increased DSI, and varying the DSI-inducing voltage step showed that the voltage dependence of DSI was like that of high-voltage-activated Ca²⁺ channels.The P- and Q-type Ca²⁺ channel blocker ω-agatoxin TK (200 nm and 1 μm) and the R- and T-type Ca²⁺ channel blocker Ni²⁺ (100 μm) reduced IPSCs without reducing DSI.The specific N-type Ca²⁺ channel antagonist ω-conotoxin GVIA (250 nm) reduced IPSC amplitudes and almost completely abolished DSI.Blocking L-type Ca²⁺ channels with nifedipine (10 μm) had no effect on IPSCs or DSI induced by our standard protocol, but reduced DSI induced by the unclamped Na⁺- and Ca²⁺-dependent spikes that occurred when 2(triethylamino)-N-(2,6-dimethylphenyl)acetamide (QX-314) was omitted from the recording pipette solution.Although intracellular Ca²⁺ stores were not measured, DSI was not affected by cyclopiazonic acid (CPA, 20–40 μm), a blocker of Ca²⁺ uptake into intracellular stores.We conclude that DSI is initiated by Ca²⁺ influx through N- and, under certain conditions, L-type Ca²⁺ channels.