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 (Mg2+O), 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 Mg2+O on myoplasmic Mg2+ buffering. The increase in Mg2+ activity observed in the presence of 5 mM Mg2+O was diminished compared with that observed in cells exposed to 0.8 mM Mg2+O. Furthermore, the increase in myoplasmic Mg2+ activity observed in the presence of 5 mM Mg2+O 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 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 Mg2+O alters cardiomyocyte myoplasmic Mg2+ activity as the result of increased Mg2+ buffering through a Ca(2+)-sensitive mechanism.
Koss
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KL
Department of Pharmacology and Toxicology, School of Medicine, Wright State University, Dayton 45435.
Grubbs
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RD
D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D002021:Buffers; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D005110:Extracellular Space / Q000378:metabolism*; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008274:Magnesium / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012966:Sodium Cyanide / Q000494:pharmacology
D000227:Adenine Nucleotides; D002021:Buffers; D007461:Iodoacetates; D008274:Magnesium; D012966:Sodium Cyanide; D002118:Calcium; D019807:Iodoacetic Acid