Relationship between transient outward K+current and Ca2+influx in rat cardiac myocytes of endo‐ and epicardial origin

1The transient outward K+current (Ito) is a major repolarizing ionic current in ventricular myocytes of several mammals. Recently it has been found that its magnitude depends on the origin of the myocyte and is regulated by a number of physiological and pathophysiological signals.2The relationship between the magnitude of Ito, action potential duration (APD) and Ca2+influx (QCa) was studied in rat left ventricular myocytes of endo‐ and epicardial origin using whole‐cell recordings and the action potential voltage‐clamp method.3Under control conditions, in response to a depolarizing voltage step to +40 mV, Itoaveraged 12.1 ± 2.6 pA pF−1in endocardial (n= 11) and 24.0 ± 2.6 pA pF−1in epicardial myocytes (n= 12; P< 0.01). APD90(90 % repolarization) was twice as long in endocardial myocytes, whereas QCainversely depended on the magnitude of Ito. L‐type Ca2+current density was similar in myocytes from both regions.4To determine the effects of controlled reductions of Itoon QCa, recordings were repeated in the presence of increasing concentrations of the Itoinhibitor 4‐aminopyridine.5Inhibition of Itoby as little as 20 % more than doubled QCain epicardial myocytes, whereas it had only a minor effect on QCain myocytes of endocardial origin. Further inhibition of Itoled to a progressive increase in QCain epicardial myocytes; at 90 % inhibition of Ito, QCawas four times larger than the control value.6We conclude that moderate changes in the magnitude of Itostrongly affect QCaprimarily in epicardial regions. An alteration of Itomight therefore allow for a regional regulation of contractility during physiological and pathophysiological adaptations.