VOLTAGE-DEPENDENCE OF G-PROTEIN-MEDIATED INHIBITION OF HIGH-VOLTAGE-ACTIVATED CALCIUM CHANNELS IN RAT PITUITARY MELANOTROPES

Dopamine D-2 receptor stimulation inhibited high-threshold, slowly inactivating (L-type) barium curents of isolated, rat pituitary melanotropes in primary culture. The extent of inhibition depended on the concentration of LY 171555 applied. Current activation in the presence of LY 171555 was described by two time constants, a fast one, also observed under control conditions, and a slow one, induced by LY 171555. The slow time constant did not depend on the concentration of LY 171555. Guanosine-5'-O-(3-thiotriphosphate) (100 mu M) induced a similar inhibition of the barium currents. Depolarizing prepulses more positive than -20 mV counteracted the inhibition induced by LY 171555 as well as guanosine-5'-O-(3-thiotriphosphate). The voltage dependence and time course of this disinhi bition were obtained. The results suggest that the slow time course of activation during current inhibition reflects a voltage-dependent conversion of the channel from the inhibited state to an available state. This voltage dependence is probably an intrinsic property of the calcium channel. The voltage-dependent rate constants of a first-order kinetic model which describes the voltage-dependent inhibition and disinhibition were estimated.