pH and voltage dependence of INa recovery kinetics in atrial cells exposed to lidocaine.

Lidocaine blocks sodium channels during depolarizations. The rate of recovery (repriming) of drug-blocked channels between depolarizations is slowed by both membrane depolarization and by acidification. This modulation of recovery kinetics was studied using a single-electrode voltage clamp on atrial cells isolated from the bullfrog. The pH dependence of recovery from inactivation, in drug-free conditions, is opposite to that observed in myelinated nerves; recovery occurs faster at higher pH levels in these cardiac preparations. The combined pH dependence and voltage dependence of repriming kinetics during lidocaine treatment can be explained by assuming that channels occupied by neutral drug can reactivate most readily at a rate that appears to be coupled to recovery from channel inactivation.