Subcellular localization of the Na+/H+ exchanger NHE1 in rat myocardium

The Na+/H+ exchanger NHE1 isoform is an integral component of cardiac intra cellular pH homeostasis that is critically important for myocardial contrac tility. To gain further insight into its physiological significance, we det ermined its cellular distribution in adult rat heart by using immunohistoch emistry and confocal microscopy. NHE1 was localized predominantly at the in tercalated disk regions in close proximity to the gap junction protein conn exin 43 of atrial and ventricular muscle cells. Significant labeling of NHE 1 was also observed along the transverse tubular systems, but not the later al sarcolemmal membranes, of both cell types. In contrast, the Na+-K+-ATPas e alpha(1)-subunit was readily labeled by a specific mouse monoclonal antib ody (McK1) along the entire ventricular sarcolemma and intercalated disks a nd, to a lesser extent, in the transverse tubules. These results indicate t hat NHE1 has a distinct distribution in heart and may fulfill specialized r oles by selectively regulating the pH microenvironment of pH-sensitive prot eins at the intercalated disks (e.g., connexin 43) and near the cytosolic s urface of sarcoplasmic reticulum cisternae (e.g., ryanodine receptor), ther eby influencing impulse conduction and excitation-contraction coupling.