CD2+ REGULATION OF THE HYPERPOLARIZATION-ACTIVATED CURRENT I-AB IN CRAYFISH MUSCLE

The effects of Cd2+ on the hyperpolarization-activated K+-mediated current called I-AB (Araque, A., and W. Buno. 1994. Journal of Neuroscience. 14:399-408.) were studied under two-electrode voltage-cramp in opener muscle fibers of the crayfish Procambarus clarkii. I-AB 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 I-AB) Cd2+ decreased the I-AB conductance (G(AB)) and shifted its voltage dependence towards hyperpolarized potentials in a similar degree, without affecting the slope of the voltage dependence. The I-AB activation time constant increased, whereas the I-AB deactivation time constant was not modified by Cd2+. The I-AB equilibrium potential (E(AB)) was unmodified by Cd2+, indicating that the selective permeability of I-AB channels was not altered. I-AB was unaffected by intracellular Cd2+. The Cd2+-regulation of I-AB did not depend on [K+](0), and the effects of [K+](0) on I-AB 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 I-AB 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 I-AB 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.