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 benefit from administration of supplemental magnesium. However, the exact mechanisms for magnesium's beneficial effects remain unknown. Lysophosphatidyl choline (LPC), an amphipathic phospholipid released from cardiac cell membranes during ischemia, increases free intracellular calcium concentrations ([Ca]i) and has been implicated as a cause of cardiac arrhythmias and coronary artery spasm during myocardial ischemia. We postulated that magnesium acts by inhibiting cellular calcium overload 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, measured in a spectrofluorometer. The increase in [Ca]i after exposure to 100 and 200 microM LPC was recorded in cells suspended in modified Dulbecco's phosphate buffered saline solution with 0.2, 2.0, and 20 mM magnesium chloride. Differences were determined by analysis of variance with P < 0.05 considered significant. LPC significantly increased [Ca]i in the 100 microM (506 +/- 76 nM) and 200 microM (675 +/- 81 nM) concentrations, 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 ineffective. LPC is a potent lipid mediator which increases myocyte [Ca]i in a concentration-dependent manner. Magnesium concentrations > or = 2.0 mM effectively antagonize the increase in [Ca]i induced by LPC. Thus, magnesium may limit intracellular calcium overload stimulated by ischemic-induced LPC release.
Prielipp
R C
RC
Department of Anesthesia, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1009, USA.
Butterworth
J F
JF
Roberts
P R
PR
Black
K W
KW
Zaloga
G P
GP
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence
D008244:Lysophosphatidylcholines; D008274:Magnesium; D002118:Calcium