title: N- and L-type calcium channel involvement in depolarization-induced suppression of inhibition in rat hippocampal CA1 cells.
abstract: 1. 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.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Lenz
authors.forename: J J
authors.initials: JJ
authors.lastname: Wagner
authors.forename: B E
authors.initials: BE
authors.lastname: Alger
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020866:omega-Conotoxin GVIA
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D007211:Indoles; D010455:Peptides; C012647:QX-314; D009532:Nickel; D020866:omega-Conotoxin GVIA; D008012:Lidocaine; D009543:Nifedipine; D002118:Calcium; C000543:cyclopiazonic acid