MAGNESIUM ANTAGONIZES THE ACTIONS OF LYSOPHOSPHATIDYL CHOLINE (LPC) IN MYOCARDIAL-CELLS - A POSSIBLE MECHANISM FOR ITS ANTIARRHYTHMIC EFFECTS

Patients with cardiac arrhythmias, ischemia, and infarction may benefi t from administration of supplemental magnesium. However, the exact me chanisms for magnesium's beneficial effects remain unknown. Lysophosph atidyl choline (LPC), an amphipathic phospholipid released from cardia c cell membranes during ischemia, increases free intracellular calcium concentrations ([Ca](i)) and has been implicated as a cause of cardia c arrhythmias and coronary artery spasm during myocardial ischemia. We postulated that magnesium acts by inhibiting cellular calcium overloa d induced by mediators such as LPC. Myocardial cells from male Sprague -Dawley rats were isolated from ventricular tissue samples and [Ca](i) determined using the fluorescent dye, fura-2/acetoxymethyl ester, mea sured in a spectrofluorometer. The increase in [Ca](i) after exposure to 100 and 200 mu M LPC was recorded in cells suspended in modified Du lbecco's phosphate buffered saline solution with 0.2, 2.0, and 20 mM m agnesium chloride. Differences were determined by analysis of variance with P < 0.05 considered significant. LPC significantly increased [Ca ](i) in the 100 mu M (506 +/- 76 nM) and 200 mu M (675 +/- 81 nM) conc entrations, compared to baseline (301 +/- 25 nM). MgCl2 at both the 2. 0 and 20 mM concentrations significantly blunted the increase in [Ca]( i) in myocardial cells exposed to LPC, whereas 0.2 mM MgCl2 was ineffe ctive. LPC is a potent lipid mediator which increases myacyte [Ca](i) in a concentration-dependent manner. Magnesium concentrations greater than or equal to 2.0 mM effectively antagonize the increase in [Ca](i) induced by LPC. Thus, magnesium may limit intracellular calcium overl oad stimulated by ischemic-induced LPC release.