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

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 Ca2+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 Ca2+loading. Perforated patch-clamp method, applied to isolated single guinea-pig ventricular myocytes, revealed that adenosine (1 m ) did not significantly reduce the magnitude of K+-induced membrane depolarization (35.7±1.7v31.0±1.1 mV in the absencevpresence of adenosine). Yet, adenosine significantly slowed the rate of K+-induced membrane depolarization (167±32.8v67.9±12.9 mV/min in the absencevpresence of adenosine) without directly affecting Ca2+, 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 Ca2+current. Indeed, in Fluo-3 loaded ventricular myocytes, imaged by laser confocal microscopy, adenosine (1 m ) prevented K+-induced intracellular Ca2+loading. The present findings indicate that adenosine slows the rate of K+-induced membrane depolarization, and reduces K+-induced intracellular Ca2+loading in ventricular myocytes. Such findings support the notion that adenosine may play a cardioprotective role in hyperkalemic cardioplegia.