High extracellular [Mg2+]-induced increase in intracellular [Mg2+] and decrease in intracellular [Na+] are associated with activation of p38 MAP kinase and ERK2 in guinea-pig heart.
High extracellular Mg(2+) concentrations ([Mg(2+)](o)) caused a remarkable concentration-dependent and reversible increase in intracellular Mg(2+) concentrations ([Mg(2+)](i)) in beating and quiescent guinea-pig papillary muscles, accompanied by a definite decrease in intracellular Na(+) concentrations ([Na(+)](i)). A change in 1 mm [Mg(2+)](o) evoked a direct change in 0.0161 mm [Mg(2+)](i) and an inverse change in 0.0263 mm [Na(+)](i). Imipramine completely abolished the high [Mg(2+)](o)-induced decrease in [Na(+)](i) and remarkably diminished the high [Mg(2+)](o)-induced increase in [Mg(2+)](i) in papillary muscles. High [Mg(2+)](o) also produced a significant activation of p38 mitogen-activated protein (MAP) kinase and extracellular signal-related kinase 2 (ERK2) that was inhibited by pretreatment with imipramine. These results suggest that the high [Mg(2+)](o)-induced increase in [Mg(2+)](i) could be coupled with the decrease in [Na(+)](i), which might involve activation of the reverse mode of Na(+)-Mg(2+) exchange, accompanied by activation of p38 MAP kinase and ERK2 in the guinea-pig heart.
Kim
Shang-Jin
SJ
Department of Physiology and Pharmacology, School of Medical Sciences, University of Bristol, Bristol, UK.
Lee
Sei-Jin
SJ
Kim
Jin-Shang
JS
Kang
Hyung-Sub
HS
D000200:Action Potentials; D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D045604:Extracellular Fluid / Q000378:metabolism*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000201:enzymology; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism*; D017736:Ion-Selective Electrodes; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D053580:Muscle Strength; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000201:enzymology*; D012964:Sodium / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D017920:Antiporters; C046250:sodium-magnesium antiporter; D012964:Sodium; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; D008274:Magnesium; D007099:Imipramine