Kinetic study of A-type current inactivation in Lymnaea neurons.

Macroscopic inactivation of A-current was studied in internally perfused Lymnaea neurons under voltage clamp conditions. Inactivation kinetics were satisfactorily described by the sum of two exponentials, suggesting the presence of two type inactivation. The kinetics of recovery from inactivation were exponential. The rate constants of the fast phase of inactivation gamma f(V) rose steeply with depolarization exposing the pronounced plateau in the range from -30 to 0 mV. The time course of inactivation in this potential range was more closely approximated with the sum of three exponentially decaying components. Calcium and hydrogen ions strongly affected the fast phase of inactivation. Calcium gave a positive shift of a part of the gamma f(V) curve on the left of the plateau. Raising the pH caused a negative shift of the right-hand branch of the gamma f(V) curve. It was shown that these effects are associated with Ca2+ and H+ binding to some specific sites of the channel protein. Two models give good fits with the experimental data. They include two pathways for fast inactivation. Calcium and hydrogen ions are assumed to selectively affect the voltage-dependent transitions related to these pathways of inactivation.