The sigma-ligand (+)-pentazocine depresses M current and enhances calcium conductances in frog melanotrophs

Gramicidin-perforated patch clamp experiments and microfluorimetric measure ments were performed to study the ionic mechanisms involved in the sigma-re ceptor-mediated stimulation of frog (Rana ridibunda) pituitary melanotrophs . The sigma-ligand (+)-pentazocine (50 mu M) depressed a sustained outward K+ current. The kinetic properties of this K+ component, investigated by an alyzing tail currents, were reminiscent of those of the M current (I-M), wi th an activation threshold close to -60 mV, a -21-mV half-maximal activatio n potential, and two-component exponential deactivation kinetics at -90 mV. (+)-Pentazocine (20 mu M) produced a 12-mV rightward shift of the activati on curve and accelerated the deactivation rate of the tail current. It is a lso demonstrated that (+)-pentazocine (20 mu M) reversibly increased both v oltage-dependent calcium conductances and internal calcium level. Altogethe r, these results suggest that the sigma-receptor-induced modulation of I-M and calcium currents likely underlies the increase of intracellular [Ca2+].