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

Abstract

High extracellular Mg2+ concentrations ([Mg2+] o) caused a remarkable concentration-dependent and reversible increase in intracellular Mg2+ concentrations ([Mg2+] 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 [Mg2+]o evoked a direct change in 0.0161 mm [Mg2+]i and an inverse change in 0.0263 mm [Na+]i. Imipramine completely abolished the high [Mg2+]o-induced decrease in [Na +]i and remarkably diminished the high [Mg 2+]o-induced increase in [Mg2+]i in papillary muscles. High [Mg2+]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 [Mg2+] o-induced increase in [Mg2+]i could be coupled with the decrease in [Na+]i, which might involve activation of the reverse mode of Na+-Mg2+ exchange, accompanied by activation of p38 MAP kinase and ERK2 in the guinea-pig heart. © 2008 The Authors.