α₁-Agonists-induced Mg²⁺ efflux is related to MAP kinase activation in the heart

The stimulation of the α₁-adrenergic receptor with phenylephrine results in the significant extrusion of Mg²⁺ from the rat heart and cardiomyocytes. Phenylephrine-induced Mg²⁺ extrusion is prevented by the removal of extracellular Ca²⁺ or by the presence of Ca²⁺-channel blockers such as verapamil, nifedipine, or (+)BAY-K8644. Mg²⁺ extrusion is almost completely inhibited by PD98059 (a MAP kinase inhibitor). The simultaneous addition of 5 mM Ca ²⁺ and phenylephrine increases the extrusion of Mg²⁺ from perfused hearts and cardiomyocytes. This Mg²⁺ extrusion is inhibited by more than 90% when the hearts are preincubated with PD98059. ERKs are activated by perfusion with either phenylephrine or 5 mM Ca²⁺. This ERK activation is inhibited by PD98059. Overall, these results suggest that stimulating the cardiac α₁-adrenergic receptor by phenylephrine causes the extrusion of Mg²⁺ via the Ca²⁺-activated, Na⁺-dependent transport pathway, and the ERKs assists in Mg ²⁺ transport in the heart.