acetylstrophanthidin and Potassium-Deficiency

Soon after a burst of triggered activity in the canine coronary sinus begins, an initial fall in maximum diastolic potential and increase in rate gives way to an increase in maximum diastolic potential, reduction in rate, and eventual quiescence. This hyperpolarization, slowing, and subsequent quiescence might result from enhanced electrogenic sodium/potassium extrusion caused by the rise in intracellular sodium concentration ([Na+]i) associated with the high rate of firing. Triggered bursts can be terminated prematurely by a sudden increase in the rate of sodium extrusion, Brief exposure to K+- free fluid is known to cause [Na+]i to rise; reactivating the pump by switching back to K+-containing fluid causes immediate hyperpolarization, and within a few seconds, quiescence. Brief periods of overdrive, also thought to increase [Na+]i, are followed by hyperpolarization, slowing and, often, by premature termination of the burst. Inhibiting the sodium/potassium pump by exposure to 2 micrometer acetylstrophanthidin or to K+-free fluid (1) prevents or delays the hyperpolarization, (2) increases the rate of triggered activity and (3) prolongs bursts of activity when bursts last less than 2.5 minutes under control conditions. In the presence of 2 micrometer acetylstrophanthidine, neither brief exposures to K+- free fluid not overdrive causes sudden, premature termination of triggered bursts. Bursts do eventually stop in the presence of pump inhibitors; however, that termination is associated with an increase in rate and a decline in maximum diastolic potential and in action potential amplitude. We conclude that electrogenic Na+ extrusion plays an important role in the spontaneous termination of triggered activity.

Topics: Animals; Coronary Vessels; Dogs; Electric Stimulation; Norepinephrine; Perfusion; Potassium Deficiency; Sodium; Strophanthidin; Time Factors