Blockade of myocardial slow inward current at low pH

Abstract

The effect of low pH on the slow cationic inward current was studied in isolated perfused embryonic chick ventricles (16-21 days old). In order to study the slow current, the fast Na+ current was inactivated by partial depolarization to about -40 mV by elevation of K+ (25 mM). Subsequent exposure of the tissue to catecholamines or methylxanthines allowed slowly rising overshooting electrical responses (the "slow response") with with accompanying contractions to be elicited by electrical stimulation. These slow responses are insensitive to tetrodotoxin and are Na+- and Ca2+-dependent. It was found that the isoproterenol- and caffeine-induced slow responses were abolished at about pH 6.1; 50% inhibition occurred at about pH 6.5. The rate of rise of the normal action potential, which is dependent on a fast Na+ current, was only slightly affected at these same pH levels; however, electromechanical uncoupling occurred, as expected from inhibition of the slow current. Therefore, the slow current was blocked at an acid pH that did not block the fast Na+ current.