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

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Abstract
1 The 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. 2 The 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. 3 Under control conditions, in response to a depolarizing voltage step to +40 mV, Ito averaged 12.1 ± 2.6 pA pF−1 in endocardial (n= 11) and 24.0 ± 2.6 pA pF−1 in epicardial myocytes (n= 12; P < 0.01). APD90 (90 % repolarization) was twice as long in endocardial myocytes, whereas QCa inversely depended on the magnitude of Ito. L‐type Ca2+ current density was similar in myocytes from both regions. 4 To determine the effects of controlled reductions of Ito on QCa, recordings were repeated in the presence of increasing concentrations of the Ito inhibitor 4‐aminopyridine. 5 Inhibition of Ito by as little as 20 % more than doubled QCa in epicardial myocytes, whereas it had only a minor effect on QCa in myocytes of endocardial origin. Further inhibition of Ito led to a progressive increase in QCa in epicardial myocytes; at 90 % inhibition of Ito, QCa was four times larger than the control value. 6 We conclude that moderate changes in the magnitude of Ito strongly affect QCa primarily in epicardial regions. An alteration of Ito might therefore allow for a regional regulation of contractility during physiological and pathophysiological adaptations.