Cd2+ regulation of the hyperpolarization-activated current IAB in crayfish muscle.
The effects of Cd2+ on the hyperpolarization-activated K(+)-mediated current called IAB (Araque, A., and W. Buño. 1994. Journal of Neuroscience. 14:399-408.) were studied under two-electrode voltage-clamp in opener muscle fibers of the crayfish Procambarus clarkii. IAB was reversibly reduced by extracellular Cd2+ in a concentration-dependent manner, obeying the Hill equation with IC50 = 0.452 +/- 0.045 mM and a Hill coefficient of 1 (determined from the maximal chord conductance of IAB). Cd2+ decreased the IAB conductance (GAB) and shifted its voltage dependence towards hyperpolarized potentials in a similar degree, without affecting the slope of the voltage dependence. The IAB activation time constant increased, whereas the IAB deactivation time constant was not modified by Cd2+. The IAB equilibrium potential (EAB) was unmodified by Cd2+, indicating that the selective permeability of IAB channels was not altered. IAB was unaffected by intracellular Cd2+. The Cd(2+)-regulation of IAB did not depend on [K+]o, and the effects of [K+]o on IAB were unchanged by Cd2+, indicating that Cd2+ did not compete with K+. Therefore, Cd2+ probably bound to a different site to that involved in the K+ permeability pathway. We conclude that Cd2+ affected the gating of IAB channels, interfering with their opening but not with their closing mechanism. The results can be explained by a kinetic model in which the binding of Cd2+ to the IAB channels would stabilize the gating apparatus at its resting position, increasing the energy barrier for the transition from the closed to the open channel states.
Araque
A
A
Instituto Cajal, CSIC, Madrid, Spain.
Cattaert
D
D
Buño
W
W
D000818:Animals; D003400:Astacoidea / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004734:Energy Metabolism / Q000187:drug effects; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*
D015221:Potassium Channels; D002104:Cadmium; D011188:Potassium