Regulation of Intracellular Free Mg2+Concentration in Isolated Rat Hearts viaβ-adrenergic and Muscarinic Receptors

Regulation of the intracellular free magnesium concentration ([Mg2+]i) was investigated in isolated rat hearts, using31P-nuclear magnetic resonance (31P-NMR). [Mg2+]iwas found to be slowly and significantly decreased during prolonged application of isoproterenol (ISO) throughβ-adrenergic receptor stimulation, and restored by subsequent washouts. The ISO-induced decrease in [Mg2+]iwas antagonized by addition of a muscarinic receptor agonist, carbachol (CCh). In the presence of atropine, CCh did not exert this effect. A water-soluble forskolin derivative, NKH477, which directly activates adenylate cyclase, also caused a decrease in [Mg2+]i, which could be antagonized by CCh, but a greater concentration was required as compared to the ISO case. The manner of [Mg2+]iregulation mimicked those noted for the action potential duration and the Ca2+channel current, in which cAMP is known to act as a second messenger. Even in the presence of a Ca2+channel blocker, verapamil, [Mg2+]iwas reversibly decreased by ISO. Changes in the intracellular ATP concentration demonstrated any clear correlation with changes in [Mg2+]i. These results suggest that [Mg2+]ican be controlled by a balance of sympathetic and parasympathetic activities. cAMP may play a key role in the [Mg2+]iregulation viaβ-adrenergic and muscarinic receptors, although some other metabolic pathways also appear to be involved. Hormonally induced changes in [Mg2+]ihave possible clinical significance.