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 approximately 1 min, was induced by depolarizing the pyramidal cell to -10 or 0 mV for 1 or 2 s. 2. 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. 3. The P- and Q-type Ca2+ channel blocker omega-agatoxin TK (200 nM and 1 microM) and the R- and T-type Ca2+ channel blocker Ni2+ (100 microM) reduced IPSCs without reducing DSI. 4. The specific N-type Ca2+ channel antagonist omega-conotoxin GVIA (250 nM) reduced IPSC amplitudes and almost completely abolished DSI. 5. Blocking L-type Ca2+ channels with nifedipine (10 microM) 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. 6. Although intracellular Ca2+ stores were not measured, DSI was not affected by cyclopiazonic acid (CPA, 20-40 microM), a blocker of Ca2+ uptake into intracellular stores. 7. We conclude that DSI is initiated by Ca2+ influx through N- and, under certain conditions, L-type Ca2+ channels.
