The Molecular Correlates of Altered Expression of Potassium Currents in Failing Rabbit Myocardium

摘要

Action potential (AP) prolongation is a hallmark of failing myocardium. Functional down regulation of K currents is a prominent feature of cells isolated from failing ventricles. The detailed changes in K current expression differ depending upon the species, the region of the heart and the mechanism of induction of heart failure. We used complementary approaches to study K current down regulation in pacing-tachycardia induced heart failure in the rabbit. The APD at 90% repolarization was significantly longer in cells isolated from failing hearts compared to controls (539 ± 162 ms failing versus 394 ± 114 control, p < 0.05). The major K currents in the rabbit heart, IK1, Ito and IK were functionally down regulated in cells isolated from failing ventricles. The mRNA levels of Kv4.2, Kv1.4, KChIP2 and Kir2.1 were significantly down regulated, while the Kv4.3, Erg, KvLQT1 and minK were unaltered in the failing compared with the control left ventricles. Significant down regulation in the long splice variant of Kv4.3 but not total Kv4.3, Kv4.2 and KChIP2 immunoreactive protein was observed in cells isolated from the failing ventricle with no change Kv1.4, KvLQT1, and in Kir2.1 immunoreactive protein levels. Multiple cellular and molecular mechanisms underlie the down regulation of K currents in the failing rabbit ventricle.