Effects of BAY K 8644 on Ca-channel currents and electrical activity in mouse melanotrophs

The effects of BAY K 8644 on both evoked and spontaneous electrical activity were studied in mouse melanotrophs. The action potential in these cells consisted of both a Na and a Ca component. BAY K 8644 greatly increased the duration of the evoked action potential apparently by enhancing the Ca component since this prolongation remained when the Na component was blocked by tetrodotoxin but was diminished by the Ca-channel antagonists Co2+ or nimodipine. In addition to its effects on the evoked action potential, BAY K 8644 sometimes caused action potentials of long duration to occur in otherwise quiescent melanotrophs, even in the presence of tetrodotoxin. These action potentials appeared to be triggered by small, depolarizing prepotentials. Voltage-clamp experiments suggested the existence of 3 types of Ca-channel currents in these cells: one low-threshold current and two high-threshold currents, one of which rapidly inactivated and another which did not. BAY K 8644 caused a shift in the I-V relation for Ca-channel current to more negative values and reduced or abolished the hump in the initial part of the I-V curve produced by the low-threshold current suggesting that BAY K 8644 selectively affects high-threshold Ca current. The action of BAY K 8644 to initiate trains of long-lasting Ca spikes and thereby increase Ca influx, might explain its secretagogue effect on the unstimulated melanotroph.