Sodium/Proton Antiporters in the Mitochondrial Inner Membrane

Abstract

The existence of membrane proteins designed for Na⁺/^H+ exchange has been established in both eukaryotic and prokaryotic systems (1), and the plethora of recent reviews (see, for example, refs. 1–3 and references therein) testifies to the perceived importance of plasma membrane Na⁺/^H+ antiporters to the physiology of the cell. A consensus is now developing that the plasmalemma of most cells contains an electroneutral Na⁺/^H+ antiporter which is inhibited by amiloride and lithium ions, and whose primary physiological role is cellular pH homeostasis. These operating characteristics have been found to be similar in a variety of cell types (2), and the conclusion has been drawn that these properties are representative of all plasma membrane Na⁺/H⁺ antiporters (3). This implies that plasma membranes contain only one type of Na⁺/H⁺ antiporter, that Na⁺ is the only physiological substrate for such antiporters, and that K⁺, in particular, is not a substrate for plasmalemmal Na⁺/^H+ antiporters. How reliable are these conclusions?