Regulation of KChIP2 potassium channel β subunit gene expression underlies the gradient of transient outward current in canine and human ventricle

Expression of four members of the KChIP family of potassium channel β subunits was examined in canine heart. Only one member of the gene family, KChIP2 , was expressed in heart. There was a steep gradient of KChIP2 mRNA expression across the canine ventricular free wall. KChIP2 mRNA was 25-fold more abundant in the epicardium than in the endocardium, and this gradient paralleled the gradient in transient outward current ( I to ) expression. In contrast, Kv4.3 potassium channel α subunit mRNA was expressed at equal levels across the ventricular wall. There was no difference in the pharmacological sensitivity of epicardial and endocardial I to channels to flecainide, suggesting that the current is produced by the same channel in the two tissues. A similar gradient of KChIP2 expression was found across the ventricular wall of human heart, but not rat heart. It is concluded that transcriptional regulation of the KChIP2 β subunit gene, rather than the Kv4.3 α subunit gene, is the primary determinant regulating the transmural gradient of I to expression in the ventricular free wall of canine and human heart.