Adenosine Slows the Rate of K +-induced Membrane Depolarization in Ventricular Cardiomyocytes: Possible Implication in Hyperkalemic Cardioplegia

Abstract

Hyperkalemic cardioplegic solutions produce cardiac arrest during open heart surgery by depolarizing the sarcolemma. A recognized adverse effect of hyperkalemic cardioplegia is the possible development of ventricular dysfunction believed to be related to intracellular Ca 2+loading, a consequence of K +-induced membrane depolarization. Adenosine has been proposed as an adjunct to hyperkalemic cardioplegic solutions. However, it is not known whether adenosine can affect K +-induced membrane depolarization, and associated intracellular Ca 2+loading. Perforated patch-clamp method, applied to isolated single guinea-pig ventricular myocytes, revealed that adenosine (1 m m) did not significantly reduce the magnitude of K +-induced membrane depolarization (35.7±1.7 v31.0±1.1 mV in the absence vpresence of adenosine). Yet, adenosine significantly slowed the rate of K +-induced membrane depolarization (167±32.8 v67.9±12.9 mV/min in the absence vpresence of adenosine) without directly affecting Ca 2+, Na +, and K +currents. Imposed ramp-pulses, with different rates (ranging from 0.33 to 0.05 V/s), but same magnitude of depolarization (100 mV), demonstrated that reduction in the rate of membrane depolarization decreases net inward Ca 2+current. Indeed, in Fluo-3 loaded ventricular myocytes, imaged by laser confocal microscopy, adenosine (1 m m) prevented K +-induced intracellular Ca 2+loading. The present findings indicate that adenosine slows the rate of K +-induced membrane depolarization, and reduces K +-induced intracellular Ca 2+loading in ventricular myocytes. Such findings support the notion that adenosine may play a cardioprotective role in hyperkalemic cardioplegia.