Lowering extracellular sodium or pH raises intracellular calcium in gastric cells

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Abstract
Summary The dependence of cytoplasmic free [Ca] (Ca i ) on [Na] and pH was assessed in individual parietal cells of intact rabbit gastric glands by microfluorimetry of fura-2. Lowering extracellular [Na] (Na o ) to 20mm or below caused a biphasic Ca i increase which consisted of both release of intracellular Ca stores and Ca entry across the plasma membrane. The Ca increase was not blocked by antagonists of Ca-mobilizing receptors (atropine or cimetidine) and was independent of the replacement cation. Experiments in Ca-free media and in Na-depleted cells indicated that neither phase was due to reversal of Na/Ca exchange. The steep dependence of the Ca i increase on Na o suggested that the response was not due to lowering intracellular [Na] (Na i ). The effects of low Na o on Ca i were also completely independent of changes in intracellular pH (pH i ). Ca i was remarkably stable during changes of pH i of up to 2 pH units, indicating that H and Ca do not share a cytoplasmic buffer system. Such large pH excursions required determination of the pH dependence of fura-2. Because fura-2 was found to decrease its affinity for Ca as pH decreased below 6.7, corrections were applied to experiments in which large pH i changes were observed. In contrast to the relative insensitivity of Ca i to changes in pH i , decreasing extracellular pH (pH o ) to 6.0 or below was found to stimulate release of intracellular Ca stores. Increased Ca entry was not observed in this case. The ability of decreases in Na o and pH o to stimulate release of intracellular Ca stores suggest interactions between Na and H with extracellular receptors.