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.

This content is only available as a PDF.