Calcium-mediated control of Ca and K currents

The inactivation of the Ca conductance (g(Ca)) both in the protozoan Paramecium and in neurons of the mollusk Aplysia has been shown to depend on the entry and accumulation of Ca ions during depolarization. This is seen as a relaxation of the current during a sustained pulse and a reduction of the inward current recorded during a subsequent depolarization. Inactivation fails to occur during depolarization in the absence of Ca entry. The amount of inactivation remaining following a depolarization is directly related to the amount of Ca accumulation during that depolarization, and the recovery from inactivation in Aplysia neurons follows a time course similar to the time course of removal of ionized Ca from the cytoplasm. Agents that speed the removal of free Ca (e.g. EGTA) also speed recovery from inactivation, and procedures that interfere with Ca entry reduce the amount of inactivation. During a steady depolarization the current relaxes (i.e., inactivates) to a low, steady level, as expected if the increment in [Ca](i) feeds back on the Ca conductance to limit the Ca current. Inactivation of the Ca conductance by prior Ca entry is accompanied by a 'depression' of the Ca-dependent potassium current, I(K(Ca)), recorded during a test depolarization. The reduction in I(K(Ca)) is related to the reduction in Ca entry and accumulation during that depolarization. Prepulses to potentials sufficiently positive to prevent Ca²⁺ entry produce strong inactivation of the voltage-dependent K current, leaving both I(Ca) and I(K(Ca)) during the test pulse undiminished. It appears then, that by producing an inactivation of g(Ca), residual intracellular free Ca²⁺ strongly limits the entry and accumulation of Ca²⁺ during a depolarization, thereby depressing the activation of I(K(Ca)). Thus, a small elevation in [Ca](i) can in fact lead to a reduction in the activation of a Ca-dependent physiological response.