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.
Davidson
J L
JL
Department of Physiology, University of British Columbia, Vancouver, Canada.
Kehl
S J
SJ
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000096:biosynthesis*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology*
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D002104:Cadmium; D013779:Tetrodotoxin; D009074:Melanocyte-Stimulating Hormones; D015032:Zinc