title: Modulation of cellular Mg2+ content in cardiac cells by α1-adrenoceptor stimulation and anti-arrhythmic agents.
abstract: Magnesium (Mg(2+)) is used pharmacologically to sedate specific forms of arrhythmias. Administration of pharmacological doses of catecholamine or adrenergic receptor agonists often results in arrhythmias onset. Results from the present study indicate that stimulation of cardiac adrenergic receptors elicits an extrusion of cellular Mg(2+) into the extracellular space. This effect occurs in both perfused hearts and isolated cells within 5-6 min following either β- or α1- adrenergic receptor stimulation, and is prevented by specific adrenergic receptors antagonists. Sequential stimulation of the two classes of adrenergic receptor results in a larger mobilization of cellular Mg(2+) provided that the two agonists are administered together or within 1-2 min from each other. A longer delay in administering the second stimulus results in the abolishment of Mg(2+) extrusion. Hence, these data suggest that the stimulation of β- and α1-adrenergic receptors mobilizes Mg(2+) from two distinct cellular pools, and that Mg(2+) loss from either pool triggers a Mg(2+) redistribution within the cardiac myocyte. At the sarcolemmal level, Mg(2+) extrusion occurs through a Na(+)/Mg(2+) exchange mechanism phosphorylated by cAMP. Administration of quinidine, a patent anti-arrhythmic agent, blocks Na(+) transport in a non-specific manner and prevents Mg(2+) extrusion. Taken together, these data indicate that catecholamine administration induces dynamic changes in total and compartmentalized Mg(2+) pools within the cardiac myocytes, and suggest that prevention of Mg(2+) extrusion and redistribution may be an integral component of the effectiveness of quinidine and possibly other cardiac antiarrhythmic agents. Confirmation of this possibility by future experimental and clinical studies might result in new patents of these compounds as Mg(2+) preserving agents.
authors.affiliation: Dept. Physiology and Biophysics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4970, USA. amr5@po.cwru.edu
authors.forename: Andrea M P
authors.initials: AM
authors.lastname: Romani
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002451:Cell Compartmentation / Q000187:drug effects; D017364:Collagenases / Q000378:metabolism; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
chemical_list: D000322:Adrenergic Agonists; D000889:Anti-Arrhythmia Agents; D018340:Receptors, Adrenergic, alpha-1; D017364:Collagenases; D008274:Magnesium