Effects of organic Ca channel blockers, Ca channel activators and omega-conotoxin on guinea-pig hippocampal CA1 neurons in vitro preparations were studied with intracellular recording methods. Most of the Ca channel blockers, such as prenylamine, D 600, flunarizine, nifedipine, cinnarizine and nicardipine (0.2-4 microM), raised the threshold for Na-dependent spike generation and decreased the amplitude of the spike afterhyperpolarization. Verapamil (5 microM) and diltiazem (5 microM) did not significantly alter the threshold and amplitude of the Na spike. Action potentials elicited in the presence of either tetrodotoxin (0.5 microM) and tetraethylammonium (20 mM) or tetrodotoxin (0.5 microM) and Ba (1.25 mM) consisted of an initial spike component followed by a long depolarization. Both responses were abolished by addition of Co (2 mM) or Cd (0.25-0.5 mM), or by superfusion with a low Ca (0.25 mM)-high Mg(15 mM) medium, indicating that the potentials resulted from Ca entry. The Ca-dependent slow depolarization was preferentially blocked by most of the organic Ca channel blockers at approximately one-third the concentrations (0.1-2 microM) which were required to shorten the Ca spike. When the cell in a solution containing tetrodotoxin (0.5 microM), Co (2 mM) and 4-aminopyridine (2 mM) was hyperpolarized and then depolarized by passing current pulses across the membrane, a transient depolarizing hump occurred on the decay phase of the electrotonic potential. This transient depolarization was abolished by Co (2 mM), Ni (2 mM) or most of the organic Ca channel blockers (0.2-5 microM). Diltiazem (5 microM) did not significantly change these Ca-dependent potentials. The evoked excitatory postsynaptic potential was very resistant to the Ca channel blockers. Approximately 2-10 times higher concentrations (0.5-3 microM) were necessary to decrease the excitatory postsynaptic potential amplitude than to shorten the Ca spike. On the other hand, the minimal concentrations and order of potencies of the Ca channel blockers for depressing the evoked inhibitory postsynaptic potential and for elevating the threshold for Na spike generation were almost the same. Dihydropyridine Ca channel activators, such as Bay K 8644, CGP 28 392 and YC 170 at low concentrations (0.1-1 microM), decreased the Ca spike, the Ca-dependent slow depolarization and the evoked synaptic potentials, while the substances augmented the Ca-dependent transient depolarization. On the other hand, omega-conotoxin (5 microM) reversibly depressed the Ca spike and slow depolarization to the same degree, without affecting the transient depolarization and the evoked excitatory or inhibitory postsynaptic potentials.(ABSTRACT TRUNCATED AT 400 WORDS)