Dihydropyridine-sensitive calcium channels in acutely-dissociated hippocampal CA1 neurons

The actions of a dihydropyridine agonist (Bay K 8644) and antagonist (nimodipine) were studied using acutely dissociated hippocampal CA1 neurons taken from young adult guinea pigs. Under whole-cell voltage-clamp conditions, these cells exhibited a single type of calcium current, which displayed peak activation at around -10 mV and which underwent little inactivation during a 100 ms depolarization. The calcium current was reversibly reduced by 10 μM nimodipine to approximately 75% of control during a step from a holding potential of -80 mV to -10 mV. Under similar conditions, 10 μM Bay K 8644 reversibly increased the current to about 150% of control. Nimodipine did not alter activation and inactivation kinetics, but Bay K 8644 caused a hyperpolarized shift of both the activation and inactivation of the calcium current. The direct effect of nimodipine on hippocampal CA1 neurons is consistent with previous data suggesting that nimodipine blocks calcium currents in central neurons and supports the hypothesis that these actions may underlie the drug's ability to improve learning.