Changes of activation and inactivation gating of the transient potassium current of rat pituitary melanotrophs caused by micromolar Cd2+ and Zn2+.

We studied the effects of Zn2+ and Cd2+ on the behaviour of IK(f), a transient outward potassium current in acutely dissociated melanotrophs of the pars intermedia of the rat pituitary gland. Micromolar concentrations of external Cd2+ or Zn2+ caused parallel and nearly equal rightward shifts along the voltage axis of the activation and steady-state inactivation curves for IK(f). The KD for the half-maximal shift of the activation curve was 278 microM for Cd2+ and 93 microM for Zn2+; the maximal shifts of the activation curve were 32.5 and 34 mV, for Cd2+ and Zn2+, respectively. The times to half-activation and half-inactivation were shifted rightward by 30-60 mV in both 500 microM Cd2+ and 500 microM Zn2+. We suggest that Cd2+ and Zn2+ interact specifically with a binding site on or electrically close to the IK(f) channel and in so doing modify the electric field "seen" by the voltage sensors.