Andrea M.P. Romani Pages 212 - 222 ( 11 )
Magnesium (Mg2+) 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 Mg2+ 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 Mg2+ 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 Mg2+ extrusion. Hence, these data suggest that the stimulation of β- and α1-adrenergic receptors mobilizes Mg2+ from two distinct cellular pools, and that Mg2+ loss from either pool triggers a Mg2+ redistribution within the cardiac myocyte. At the sarcolemmal level, Mg2+ extrusion occurs through a Na+/Mg2+ exchange mechanism phosphorylated by cAMP. Administration of quinidine, a patent anti-arrhythmic agent, blocks Na+ transport in a non-specific manner and prevents Mg2+ extrusion. Taken together, these data indicate that catecholamine administration induces dynamic changes in total and compartmentalized Mg2+ pools within the cardiac myocytes, and suggest that prevention of Mg2+ 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 Mg2+ preserving agents.
Arrhythmias, Mg2+ extrusion, heart, cardiac ventricular myocytes, adrenergic agonist, catecholamine, quinidine, patents
Dept. Physiology and Biophysics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4970, USA.