Muscarinic stimulation induces release of Mg 2؉ from an intracellular pool in rat sublingual mucous acini (Zhang, G. H., and Melvin, J. E. (1992) J. Biol. Chem. 267, 20721-20727). In the present study we examined the interdependence of Mg 2؉ mobilization on intracellular Na ؉ and Ca 2؉ by monitoring the intracellular free concentrations of Na ؉ ([Na ؉ ] i ), Mg 2؉ ([Mg 2؉ ] i ), and Ca 2؉ ([Ca 2؉ ] i ) using ion-sensitive fluorescent indicators. Gramicidin increased the intracellular

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... ons of all three ions. Comparable to agonist-stimulated mobilization of Mg 2؉ , the gramicidin-induced [Mg 2؉ ] i increase was independent of extracellular Mg 2؉ indicating release of Mg 2؉ from an intracellular pool. Clamping the [Ca 2؉ ] i near 30 nM with the Ca 2؉ -selective chelator BAPTA failed to alter the [Na ؉ ] i or [Mg 2؉ ] i increases generated by gramicidin. In contrast, depletion of intracellular Na ؉ markedly suppressed the muscarinic-stimulated [Mg 2؉ ] i increase, whereas the [Ca 2؉ ] i increase was similar to that seen in physiological extracellular Na ؉ . These results revealed that intracellular Mg 2؉ mobilization did not directly relate to the [Ca 2؉ ] i , but required an increase in [Na ؉ ] i . Consistent with this hypothesis, increasing [Na ؉ ] i by activating Na ؉ influx via the Na ؉ /H ؉ exchanger also increased the [Mg 2؉ ] i . The Na ؉ /Mg 2؉ exchange inhibitor quinidine suppressed both the gramicidin-and muscarinic-induced discharge of internal Mg 2؉ . These results suggest that release of Mg 2؉ from an intracellular pool is mediated by a Na ؉dependent Mg 2؉ transport mechanism in salivary acinar cells. . 1 The abbreviations used are: [Na ϩ ] i , [Mg 2ϩ ] i , and [Ca 2ϩ ] i , intracellular free concentrations of sodium, magnesium, and calcium, respec-