Effect of acute and prolonged alcohol administration on Mg2+ homeostasis in cardiac cells

• Chronic exposure to ethanol markedly depleted cardiac myocytes of cellular magnesium.
• Acute ethanol exposure induced a time- and dose-dependent manner Mg2+ loss from cardiac cells.
• Inhibition of cytP4502E1 prevents ethanol effect on cellular magnesium.
• Magnesium extrusion across the sarcolemma occurs via the amiloride-inhibited Na+/Mg2+ exchanger.

Alcoholic cardiomyopathy represents a major clinical complication in chronic alcoholics. Previous studies from our laboratory indicate that acute and chronic exposure of liver cells to ethanol results in a major loss of cellular Mg2+ as a result of alcohol oxidation. We investigated whether exposure to ethanol induces a similar Mg2+ loss in cardiac cells. The results indicate that chronic exposure to a 6% ethanol-containing diet depleted cardiac myocytes of >25% of their cellular Mg2+ content. Acute ethanol exposure, instead, induced a time- and dose-dependent manner of Mg2+ extrusion from perfused hearts and collagenase-dispersed cardiac ventricular myocytes. Pretreatment with chlormethiazole prevented ethanol-induced Mg2+ loss to a large extent, suggesting a role of ethanol oxidation via cyP4502E1 in the process. Magnesium extrusion across the sarcolemma occurred via the amiloride-inhibited Na+/Mg2+ exchanger. Taken together, our data indicate that Mg2+ extrusion also occurs in cardiac cells exposed to ethanol as a result of alcohol metabolism by cyP4502E1. The extrusion, which is mediated by the Na+/Mg2+ exchanger, only occurs at doses of ethanol ≥0.1%, and depends on ethanol-induced decline in cellular ATP. The significance of Mg2+ extrusion for the onset of alcoholic cardiomyopathy remains to be elucidated.