Effects of T-type, L-type, N-type, P-type, and Q-type calcium channel blockers on stimulus-induced pre- and postsynaptic calcium fluxes in rat hippocampal slices.

Abstract

The contribution of T-, L-, N-, P-, and Q-type Ca2+ channels to pre- and postsynaptic Ca2+ entry during stimulus-induced high neuronal activity in area CA1 of rat hippocampal slices was investigated by measuring the effect of specific blockers on stimulus-induced decreases in extracellular Ca2+ concentration ([Ca2+]o). [Ca2+]o was measured with ion-selective electrodes in stratum radiatum (SR) and stratum pyramidale (SP), while Ca2+ entry into neurons was induced with stimulus trains (20 Hz for 10 s) alternately delivered to SR and the alveus, respectively. The [Ca2+]o decreases recorded in SR in response to SR stimulation represented mainly presynaptic Ca2+ entry (Capre), while [Ca2+]o decreases recorded in SP in response to alvear stimulation were predominantly based on postsynaptic Ca2+ entry (Capost). Ethosuximide and trimethadione were ineffective in concentrations up to 1 mM. At 10 mM, they reduced Capost and, much less, also Capre. Nimodipine (25 microM) reduced Capost and, to a minor extent, Capre. omega-Agatoxin IVA (0.4-1 microM) and omega-contoxin MVIIC (1 microM) also reduced both Capre and Capost, but with a stronger action on Capre. omega-Conotoxin GVIA (3-8 microM) reduced Capost without effect on Capre. We conclude that during stimulus-induced, high-frequency neuronal activity Capost is carried by P/Q-, N-, and L- type channels and probably a further channel type different from these channels. Capre includes at least P/Q- and possibly L-type channels. N-type channels did not contribute to Capre in our experiments. Since ethosuximide and trimethadione were only effective in high concentrations, their action may be unspecific. Thus, T-type channels do not seem to play a major part in Ca2+ entry in this situation.