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Am J Physiol Heart Circ Physiol 276: H709-H717, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 2, H709-H717, February 1999

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

Kevin Petrecca1, Roxana Atanasiu1, Sergio Grinstein2, John Orlowski1, and Alvin Shrier1

1 Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6; and 2 Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8

The Na+/H+ exchanger NHE1 isoform is an integral component of cardiac intracellular pH homeostasis that is critically important for myocardial contractility. To gain further insight into its physiological significance, we determined its cellular distribution in adult rat heart by using immunohistochemistry and confocal microscopy. NHE1 was localized predominantly at the intercalated disk regions in close proximity to the gap junction protein connexin 43 of atrial and ventricular muscle cells. Significant labeling of NHE1 was also observed along the transverse tubular systems, but not the lateral sarcolemmal membranes, of both cell types. In contrast, the Na+-K+-ATPase alpha 1-subunit was readily labeled by a specific mouse monoclonal antibody (McK1) along the entire ventricular sarcolemma and intercalated disks and, to a lesser extent, in the transverse tubules. These results indicate that NHE1 has a distinct distribution in heart and may fulfill specialized roles by selectively regulating the pH microenvironment of pH-sensitive proteins at the intercalated disks (e.g., connexin 43) and near the cytosolic surface of sarcoplasmic reticulum cisternae (e.g., ryanodine receptor), thereby influencing impulse conduction and excitation-contraction coupling.

ion transporters; pH regulation; subcellular; confocal microscopy


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