On the mechanism of overdrive suppression in the guinea pig sinoatrial node

Factors underlying overdrive suppression were studied in guinea pig sinoatrial node perfused in vitro. Overdrive (1) is followed by a short suppression and a transient decrease in maximum diastolic potential (Emax); (2) causes an immediate decrease and then a reincrease in force followed after overdrive by a transient overshoot; (3) may induce a marked suppression in high [Ca]0, which is a function of the rate and duration of overdrive and is not affected by tetrodotoxin or atropine; (4) in the presence of acetylcholine (ACh), decreases Emax and causes a longer suppression, which may be associated to a transient hyperpolarization; (5) can be initiated periodically by spontaneous beats and the cycles are abolished by calcium antagonists but not by atropine; (6) in high [Ca]0 (but not in ACh) is followed by an oscillatory potential, the amplitude of which depends of the characteristics of overdrive; (7) does not cause suppression in zero [Ca]0; (8) may cause suppression that is due to failure of conduction; and (9) may be followed by a prolonged transient hyperpolarization in the presence of ACh and Cs. Thus, the sinoatrial node, intracellular calcium accumulation enhances overdrive suppression and causes periodic suppression of spontaneous cyclic rhythms. These calcium actions are direct and not related to a potentiation of ACh effects. The elimination of diastolic depolarization by ACh and Cs reveals an overdrive-induced hyperpolarization possibly related to an electrogenic Na extrusion.