Kinetics of calcium‐dependent inactivation of calcium current in voltage‐clamped neurones of Aplysia californica.

Abstract

Ca currents flowing during voltage-clamp depolarizations were examined in axotomized Aplysia neurons under conditions that virtually eliminated other currents. Moderate to large currents exhibited a 2-component time course of relaxation that can be approximated reasonably well by the sum of 2 exponentials. The rapid phase (.tau.1 .apprxeq. 70 ms at 0 mV) plus the slower phase (.tau.2 .apprxeq. 300 ms at 0 mV) ride upon a steady, non-inactivating current IINF. The relation of inactivation to prior Ca2+ entry was essentially linear for small currents, but decreased in slope with time during strong currents. The relation also became shallower with increasing depolarization, suggesting an apparent decrease in the efficacy of Ca in causing inactivation at more positive potentials. The basic kinetics of Ca current inactivation along with experimentally induced changes in those kinetics were simulated with a binding model in which inactivation develops during current flow as a function of the entry and accumulation of free Ca2+. A single Ca-mediated process can account for the 2-component time course of inactivation. The nearly bi-exponential shape need not arise from 2 separate processes. The 2-component time course emerges as a consequence of a postulated hyperbolic reaction between diminishing probability of channels remaining open and the accumulation of intracellular free Ca2+. The occurrence of a single- or a 2-component time course of inactivation thus appears to depend on the levels of internal free Ca2+ traversed during current flow.