ELEVATED EXTRACELLULAR MG2+ INCREASES MG2+ BUFFERING THROUGH A CA-DEPENDENT MECHANISM IN CARDIOMYOCYTES

To investigate the physiological basis for the pharmacological action of extracellular magnesium (Mg-o(2+)), cultured ventricular myocytes were exposed to either 0.8 mM (physiological) or 5.0 mM Mg2+ (therapeutic concentration) in the presence and absence of metabolic inhibitors. Metabolic inhibition, induced with 1 mM iodoacetate and 1 mM NaCN, was used to liberate Mg2+ from MgATP into the myoplasm, permitting examination of the role of elevated Mg-o(2+) on myoplasmic Mg2+ buffering. The increase in Mg2+ activity observed in the presence of 5 mM Mg-o(2+) was diminished compared with that observed in cells exposed to 0.8 mM Mg-o(2+). Furthermore, the increase in myoplasmic Mg2+ activity observed in the presence of 5 mM Mg-o(2+) was identical to that reported previously in the absence of extracellular Ca2+. Fura 2 measurements of Ca2+ activity in these experimental conditions suggested that the Ca2+ permeability of cells exposed to 5 mM Mg2+ was less than that observed for cells exposed to 0.8 mM Mg2+. Using the Mg2+ buffer coefficient to quantitate cellular Mg2+ buffering, we observed a 63% increase in Mg2+ buffering in cells exposed to 5 mM Mg2+ compared with cells exposed to 0.8 mM Mg2+. This study demonstrates that elevated Mg-o(2+) alters cardiomyocyte myoplasmic Mg2+ activity as the result of increased Mg2+ buffering through a Ca2+-sensitive mechanism.