Differential Structure of Atrial and Ventricular K ATP

Abstract

The isoform-specific structure of the ATP-sensitive potassium (KATP) channel endows it with differential fundamental properties, including physiological activation and pharmacology. Numerous studies have convincingly demonstrated that the pore-forming Kir6.2 (KCNJ11) and regulatory SUR2A (ABCC9) subunits are essential elements of the sarcolemmal KATP channel in cardiac ventricular myocytes. Using a novel antibody directed against the COOH terminus of SUR1 (ABCC8), we show that this KATP subunit is also expressed in mouse myocardium and is the dominant SUR isoform in the atrium. This suggests differential sarcolemmal KATP composition in atria and ventricles, and, to test this, KATP currents were measured in isolated atrial and ventricular myocytes from wild-type and SUR1−/− animals. KATP conductance is essentially abolished in SUR1−/− atrial myocytes but is normal in SUR1−/− ventricular myocytes. Furthermore, pharmacological properties of wild-type atrial KATP match closely the properties of heterologously...