K 2p 3.1 protein is expressed as a transmural gradient across the rat left ventricular free wall

Abstract

Introduction: K 2p 3.1, also known as TASK-1, is a twin-pore acid-sensitive repolarizing K + channel, responsible for a background potassium current that significantly contributes to setting the resting membrane potential of cardiac myocytes. Inhibition of I K2p3.1 alters cardiac repolarization and is proarrhythmogenic. In this study, we have examined the expression of K 2p 3.1 and function of this channel in tissue and myocytes from across the left ventricular free wall. Methods and Results: Using fluorescence immunocytochemistry, the expression of K 2p 3.1 protein in myocytes from the subendocardial region was found to be twice (205% ± 13.5%) that found in myocytes from the subepicardial region of the left ventricle (100% ± 5.3%). The left ventricular free wall exhibited a marked transmural gradient of K 2p 3.1 protein expression. Western blot analysis confirmed significantly higher K 2p 3.1 protein expression in subendocardial tissue (156% ± 2.5%) than subepicardial tissue (100% ± 5.0%). However, there was no difference in K 2p 3.1 messenger RNA expression. Whole-cell patch clamp identified I K2p3.1 current density to be significantly greater in myocytes isolated from the subendocardium (7.66 ± 0.53 pA/pF) compared with those from the subepicardium (3.47 ± 0.74 pA/pF). Conclusions: This is the first study to identify a transmural gradient of K 2p 3.1 in the left ventricle. This gradient has implications for understanding ventricular arrhythmogenesis under conditions of ischemia but also in response to other modulatory factors, such as adrenergic stimulation and the presence of anesthetics that inhibits or activates this channel.