Regulation of Mg2+ release in guinea pig heart and isolated ventricular myocytes by alpha1-adrenergic stimulation

ABSTRACT

Mg2+ is the fourth most abundant cation in cellular organisms. Although the biological chemistry and the physiological roles of the magnesium ion were well known, the regulation of intracellular Mg2+ in mammalian cells is not fully understood. More recently, however, the mechanism of Mg2+ mobilization by hormonal stimulation has been investigated in hearts and in myocytes. In this work we have investigated the regulation mechanism responsible for the Mg2+ mobilization induced by alpha1-adrenoceptor stimulation in perfused guinea pig hearts or isolated myocytes. The Mg2+ content of the perfusate or the supernatant was measured by atomic absorbance spectrophotometry. The elimination of Mg2+ in the medium increased the force of contraction of right ventricular papillary muscles. Phenylephrine also enhanced the force of contraction in the presence of Mg2+/-free medium. alpha1-Agonists such as phenylephrine were found to induce Mg2+ efflux in both perfused hearts or myocytes. This was blocked by prazosin, a alpha1-adrenoceptor antagonist. Mg2+ efflux by phenylephrine was amplified by Na+ channel blockers, an increase in extracellular Ca2+ or a decrease in extracellular Na+. By contrast, the Mg2+ influx was induced by verapamil, nifedipine, ryanodine, lidocaine or tetrodotoxin in perfused hearts, but not in myocytes. W7, a Ca2+/calmodulin antagonist, completely blocked the phenylephrine-, A23187-, veratridine-, Ca2+/-induced Mg2+ efflux in perfused hearts or isolated myocytes. In addition, Mg2+ efflux was induced by W7 in myocytes but not in perfused heart. In conclusion, An increase in Mg2+ efflux by alpha1-adrenoceptor stimulation in hearts can be through IP3 and Ca2+/-calmodulin dependent mechanism.