DOPAMINE INHIBITS 2 CHARACTERIZED VOLTAGE-DEPENDENT CALCIUM CURRENTS IN IDENTIFIED RAT LACTOTROPH CELLS

The effects of dopamine (DA) on voltage-dependent Ca2+currents were investigated in cultured rat lactotroph cells using the patch clamp recording technique. Each recorded cell was identified by the reverse hemolytic plaque assay. In the whole-cell configuration, two types of Ca2+currents, L and T, were characterized on the basis of their kinetics, voltage sensitivity, and pharmacology. The L component had a threshold of -25 mV, showed little inactivation during a 150-msec voltage step, and was maximal at +10 mV. Cadmium ions (100 µM) significantly reduced its amplitude (75%). The T component was activated at a membrane potential close to —50 mV, was maximal at —10 mV, and showed a voltage-dependent inactivation between —90 and —30 mV. It was quickly inactivated during a maintained depolarization (time constant, 27 ms at —30 mV) and was strongly reduced (80%) by nickel ions (100 µM). Bath application of DA (10 nM) caused a markedly general depression of inward Ca2+currents, acting differently on the T- and L-type currents. DA application shifted the voltage-dependence of the L-type current activation toward depolarization values (8 mV) without modifying its time- and voltage-dependent inactivation. In contrast, DA enhanced the inactivation of the T-type current by accelerating its time-dependent inactivation (25% decrease in the time constant of inactivation) and by shifting the voltagedependence of the T-type current inactivation toward hyperpolarizing values (-63 mV in control vs. —77 mV in the presence of DA). These effects of DA were dose-dependent and involved the activation of a D2receptor type. They were mimicked by bromocriptine application (10 nM), whereas sulpiride (100 nM) blocked the DA-evoked response. The D1antagonist SCH 23390 was ineffective up to 100 µM. All of these DA-induced modifications in Ca2+currents were abolished using a GTP-free pipette solution or after pretreatment of cells with pertussis toxin, suggesting that DA can regulate the function of Ca2+channels through GTP-binding proteins (G-proteins). Our results show that DA acts simultaneously by reducing both voltage-dependent Ca2+currents on lactotroph cells. Thus, DA reduces the entry of Ca2+ions across the surface membrane and thereby influences electrical activity and the cytosolic free Ca2+concentration involved in both basal and evoked PRL release. © 1990 by The Endocrine Society.