Dopamine-induced inhibition of action potentials in cultured frog pituitary melanotrophs is mediated through activation of potassium channels and inhibition of calcium and sodium channels.

A patch-clamp study was conducted in order to investigate the effects of dopamine on the ionic currents in cultured frog melanotrophs. Brief applications of dopamine (1 microM) hyperpolarized the cell and inhibited the spontaneous action potentials. The hyperpolarization was accompanied by an increase in membrane conductance. Under voltage clamp, dopamine evoked a net outward current. The dopamine-induced outward current was negligible at the equilibrium potential for potassium ions. It was also observed that dopamine increased the intensity of a voltage-dependent outward potassium current monitored by constant depolarizing pulses. In addition, voltage-dependent L- and N-like calcium currents and sodium current were reduced. In the cell-attached configuration, two distinct channel types were activated and one channel type was blocked by dopamine exposure to the extrapatch membrane, which indicates the involvement of an intracellular factor in the signal transduction pathway. A higher conductance channel (100 pS) was characterized by a very low basal activity which rapidly increased upon dopamine application. A lower conductance channel (30 pS) displayed a basal activity with frequent opening events, and a delayed (30-40 s) increase of activity in response to dopamine. Both currents reversed at a deduced potential corresponding to the equilibrium potential for potassium ions. The channel type inhibited by dopamine had a low conductance of 15 pS. The inhibition of the electrical activity induced by dopamine was totally blocked by the D2 receptor antagonist S(-)-sulpiride (1 microM) but was not affected by the D1 receptor antagonist SKF-83566 (1 microM). It is concluded that dopamine activates potassium channels and inhibits calcium and sodium channels in frog melanotrophs. The results also indicate that stimulus-response coupling is mediated by intracellular messenger system(s).