Calcium–hydrogen exchange by the plasma membrane Ca-ATPase of voltage-clamped snail neurons

The submicromolar levels of free Ca(2+) ions in animal cells are believed to be maintained in the long term by two different plasma membrane transport mechanisms. These are Na-Ca exchange, driven by the sodium gradient, and a Na-independent Ca pump, driven by ATP. There is good evidence from red blood cells, and indirect evidence from other non-neuronal preparations, that the Ca-ATPase exchanges internal Ca(2+) for external H(+). Although Ca extrusion from nerve cells is inhibited by high external pH, there as yet is no evidence for the counter-transport of H(+). We have used both pH- and calcium-sensitive microelectrodes on the cell surface, and the Ca indicator fura-2 intracellularily, to investigate how snail neurons regulate cytoplasmic free Ca(2+). We now report that in snail neurons the recovery of intracellular Ca(2+) after an increase coincides with both the expected increase in surface Ca(2+) and a decrease in surface H+. Recovery of intracellular Ca and the changes in surface pH and Ca are all blocked by intracellular vanadate. We conclude that snail neurons regulate intracellular Ca mainly by a Ca-H ATPase, and suggest that this Ca-H exchange may account for many of the reported extracellular pH changes seen with neuronal excitation.