N-TYPE AND L-TYPE CALCIUM-CHANNEL INVOLVEMENT IN DEPOLARIZATION-INDUCED SUPPRESSION OF INHIBITION IN RAT HIPPOCAMPAL CA1 CELLS

1. We investigated depolarization-induced suppression of inhibition (D SI) under whole-cell voltage clamp in CA1 pyramidal neurons of rat hip pocampal slices. DSI, a transient reduction in monosynaptic evoked GAB A(A)ergic IPSCs lasting for similar to 1 min, was induced by depolariz ing the pyramidal cell to -10 or 0 mV for 1 or 2 s. 2. Raising extrace llular Ca2+ concentration increased DSI, and varying the DSI-inducing voltage step showed that the voltage dependence of DSI was like that o f high-voltage-activated Ca2+ channels. 3. The P- and Q-type Ca2+ chan nel blocker omega-agatoxin TK (200 nM and 1 mu M) and the R- and T-typ e Ca2+ channel blocker Ni2+ (100 mu M) reduced IPSCs without reducing DSI. 4. The specific N-type Ca2+ channel antagonist omega-conotoxin GV IA (250 nM) reduced IPSC amplitudes and almost completely abolished DS I. 5. Blocking L-type Ca2+ channels with nifedipine (10 mu M) had no e ffect on IPSCs or DSI: induced by our standard protocol, but reduced D SI induced by the unclamped Na+- and Ca2+ dependent spikes that occurr ed when 2(triethylamino) -N-(2,6 -dimethylphenyl)acetamide (QX-314) wa s omitted from the recording pipette solution. 6. Although intracellul ar Ca2+ stores were not measured, DSI was not affected by cyclopiazoni c acid (CPA, 20-40 mu M), 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.