Gramicidin-perforated patch clamp experiments and microfluorimetric measurements were performed to study the ionic mechanisms involved in the sigma-receptor-mediated stimulation of frog (Rana ridibunda) pituitary melanotrophs. The sigma-ligand (+)-pentazocine (50 microM) depressed a sustained outward K(+) current. The kinetic properties of this K(+) component, investigated by analyzing tail currents, were reminiscent of those of the M current (I(M)), with an activation threshold close to -60 mV, a -21-mV half-maximal activation potential, and two-component exponential deactivation kinetics at -90 mV. (+)-Pentazocine (20 microM) produced a 12-mV rightward shift of the activation curve and accelerated the deactivation rate of the tail current. It is also demonstrated that (+)-pentazocine (20 microM) reversibly increased both voltage-dependent calcium conductances and internal calcium level. Altogether, these results suggest that the sigma-receptor-induced modulation of I(M) and calcium currents likely underlies the increase of intracellular [Ca(2+)].