Concordant expression of KChIP2 mRNA, protein and transient outward current throughout the canine ventricle

Expression of the transient outward K⁺ current (I_to) was analysed in nine different regions of the canine ventricle. In addition to the previously described transmural gradients in the right and left ventricular free walls, an inverted U-shaped pattern of I_to expression was observed in the interventricular septum. The mRNA and protein expression for the K⁺ channel β subunit KChIP2 were examined in the same tissues. The KChIP2 protein levels closely matched mRNA expression in all regions of the ventricle and paralleled the density of I_to. The global pattern of gene expression in human epicardial and endocardial tissue was examined using microarrays. Only 0.1% of the genes expressed in the human ventricle displayed the same expression pattern as the KChIP2 gene in left ventricle. It is unlikely, therefore, that the reported distribution of KChIP2 protein within the ventricle can be explained by a cross-reaction of the anti-KChIP2 antibody with a different protein. It is concluded that transcriptional regulation of the KChIP2 gene is a primary determinant of I_to expression in heart.