FUNCTIONAL IMPAIRMENT OF CARDIAC TRANSIENT OUTWARD K+ CURRENT AS A RESULT OF ABNORMALLY ALTERED CELLULAR ENVIRONMENT

SUMMARY Physiological functions of cardiac cells require a normal cellular environment. Under pathological conditions, there is a loss of normal cellular environment due to metabolic perturbations and other abnormalities. To test the hypothesis that cellular environmental stresses can create an electrophysiological substrate for electrical disorders in the heart, we investigated the effects of hypoxia, acidosis and ischaemia on transient outward K+ current (Ito) in single canine ventricular myocytes. The Ito was studied because it plays a critical role in initiating cardiac repolarization and, thereby, arrhythmias. It was found that Ito was significantly depressed by some 30% under hypoxic conditions relative to that in a normal cellular environment with normal Tyrode's solution. Acidosis created by lowering the pH of the external solution from 7.4 to 7.2 produced a substantial (approximately 35%) reduction of the Ito amplitude. A marked impairment of Ito function was consistently observed in ischaemic hearts in the canine coronary artery ligation model, with an approximate 30% decrease in the size of Ito. Importantly, the impairment of Ito under these environmental stresses was largely reversible following restoration to normal conditions. The results of the present study suggest that Ito is susceptible to changes in the cellular environment and the functional impairment of Ito under environmental stresses contributes to arrhythmias under relevant pathological conditions of the heart.