Nifedipine blocks calcium-dependent cholinergic depolarization in the guinea pig hippocampus

The possibility that cholinergic stimulation might directly activate a receptor-operated Ca2+ channel was investigated in the CA1 region of guinea pig hippocampus using intracellular recording techniques. Two cholinergic responses were studied: (1) the plateau depolarization evoked by cholinergic stimulation in the presence of Ba2+; and (2) the Ca2(+)-dependent component of membrane depolarization. Both of these responses were blocked by 1-5 microM of nifedipine, a blocker of voltage-dependent L-type Ca2+ channels. In addition, the plateau response was mimicked by direct postsynaptic depolarization in the presence of Ba2+. We conclude that cholinergic stimulation does not directly activate a Ca2+ conductance in these neurons, but rather leads to the indirect activation of L channels which may be located both pre- and postsynaptically.