Mechanisms responsible for the increased magnesium efflux associated with raised [Na+]o in the isolated perfused rat heart.

The intracellular and extracellular concentration gradient of ionized magnesium (Mg(2+)) in the heart appears to be small, but large electrochemical gradients exist which will tend to move Mg(2+) into the cell. Since the myocardial plasma membrane is not impermeable to Mg(2+), mechanisms must exist to either inhibit influx or promote efflux of Mg(2+) in order to preserve steady state intracellular Mg(2+) concentration, [Mg(2+)]i. In this study the effects of extracellular sodium concentration ([Na+]o) on Mg(2+) transport were investigated in the isolated perfused rat heart. When [Na+]o was increased, using either sodium chloride (NaCl) or sodium isethionate (36.3 mM), a large Mg(2+) efflux and concomitant increase in the amplitude of contraction were observed. The raised NaCl-evoked Mg(2+) efflux was significantly inhibited by amiloride hydrochloride (10(-3) M and 10(-5) M) and by the beta-adrenergic antagonist, propranolol (10(-5) M). Large Mg(2+) effluxes and concomitant increases in the amplitude of contraction were also observed during perfusion of the heart with choline chloride (36.3 mM) and sucrose (54.45 and 72.6 mM). The effect due to sucrose appeared to be concentration-dependent. Raised NaCl had no significant effect on lactate dehydrogenase activity. Although there seems to be an amiloride and propranolol sensitive component to Mg(2+)efflux in the mammalian heart, the changes in Mg(2+) efflux and contractile activity observed in these experiments may, to a large extent, be osmotic in origin.