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 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.