High voltage-activated Ca(2+) channel subtypes triggering GABA release from nerve terminals (boutons) projecting to rat hippocampal CA1 pyramidal neurons were studied. Evoked GABAergic inhibitory postsynaptic currents (eIPSCs) were recorded in response to focal stimulation of single boutons in mechanically dissociated neurons and in response to stimulation of nerve bundle in slice preparations. Nilvadipine (3 micro M), an L-type Ca(2+) channel blocker, completely inhibited eIPSCs evoked by stimulation of single boutons, but had no effect on eIPSCs evoked by stimulation of nerve bundle at low frequencies. Nilvadipine (3 micro M) did, however, prevent the potentiation of eIPSC amplitude following high-frequency stimulation of nerve bundles in the slice preparation. omega-Conotoxin-GVIA (3 micro M), an N-type Ca(2+) channel blocker, and omega-agatoxin-IVA (0.3 micro M), a P/Q-type Ca(2+) channel blocker, completely inhibited single bouton evoked eIPSCs in 33.3 and 83.3% of recordings, respectively. In response to low-frequency nerve bundle stimulation in the slice preparation, omega-conotoxin-GVIA (3 micro M), omega-agatoxin-IVA (0.1 micro M) both partially reduced eIPSC amplitude, with the residual component being abolished by Cd(2+) (0.1 mM). From these results, the following hypotheses could be drawn. (1). The distribution of P/Q- and N-type channels at a single bouton is nonuniform. (2. When a focal stimulation is applied to a single bouton, L-type channels play a significant role in a generation of an action potential which subsequently activates P/Q- and N-type channels at GABA release sites. (3). Action potentials conducted through axons in the slice preparation are sufficient to depolarize the bouton membrane, even when L-type channels are suppressed.