title: Effect of acute and prolonged alcohol administration on Mg(2+) homeostasis in cardiac cells.
abstract: 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 Mg(2+) as a result of alcohol oxidation. We investigated whether exposure to ethanol induces a similar Mg(2+) loss in cardiac cells. The results indicate that chronic exposure to a 6% ethanol-containing diet depleted cardiac myocytes of >25% of their cellular Mg(2+) content. Acute ethanol exposure, instead, induced a time- and dose-dependent manner of Mg(2+) extrusion from perfused hearts and collagenase-dispersed cardiac ventricular myocytes. Pretreatment with chlormethiazole prevented ethanol-induced Mg(2+) 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(+)/Mg(2+) exchanger. Taken together, our data indicate that Mg(2+) 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(+)/Mg(2+) exchanger, only occurs at doses of ethanol ≥0.1%, and depends on ethanol-induced decline in cellular ATP. The significance of Mg(2+) extrusion for the onset of alcoholic cardiomyopathy remains to be elucidated.
authors: Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: amr5@po.cwru.edu.
authors: Andrea M P
authors: AM
authors: Romani
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D065691:Cytochrome P-450 CYP2E1 Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology; D006706:Homeostasis / Q000187:drug effects; D007474:Ion Exchange; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D002492:Central Nervous System Depressants; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D000431:Ethanol; D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; D019392:Cytochrome P-450 CYP2E1; D008274:Magnesium
keywords: Amiloride; Cardiac ventricular myocytes; Ethanol; Magnesium extrusion; cyP4502E1