Regulation of Na ‐ Ca Exchange

The regulation of the Na-Ca exchanger is a subject that has received much attention in the past decade. In general, the importance of regulatory processes is that they are able to modify the activity of carriers, pumps, and channels, without necessarily changing the driving force of the transported ions. Several physiological ligands and experimental procedures are known to influence the exchange activity. They include nucleotides, intracellular Ca2+ and Mg2+, hydrogen ions, monovalent cations, orthophosphate, redox potential, and modifications of the lipid and protein composition of the plasma membrane (see Reeves' and DiPolo & Beaugi2 for references). At present we do not have a clear picture of how the Na-Ca exchange is actually regulated, nor the physiological role, if any, of these modifiers. An additional complexity is given by the fact that the response to several of the aforementioned ligands varies with the preparation used. Particularly illustrative are the different effects found in intact cells or intact plasma membrane (injected, perfused, and dialyzed cells and giant excised patches) compared with isolated membrane vesic l e ~ . ' , ~ . ~ Because many of the contributors to this publication will deal with several regulatory features of the Na-Ca exchanger, we will restrict ourselves to the two major in vivo modulators: ATP and intracellular ionized Ca.