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


Corresponding author B. E. Alger: Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA. Email: balger@umaryland.edu


  • 1We 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.
  • 2Raising 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.
  • 3The 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.
  • 4The specific N-type Ca2+ channel antagonist ω-conotoxin GVIA (250 nm) reduced IPSC amplitudes and almost completely abolished DSI.
  • 5Blocking 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.
  • 6Although 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.
  • 7We conclude that DSI is initiated by Ca2+ influx through N- and, under certain conditions, L-type Ca2+ channels.