Regulation of Mg²⁺ release in guinea pig heart and isolated ventricular myocytes by α₁-adrenergic stimulation

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 α₁- 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. α₁-Agonists such as phenylephrine were found to induce Mg²⁺ efflux in both perfused hearts or myocytes. This was blocked by prazosin, a α₁-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 pheylephrine-, 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 α₁-adrenoceptor stimulation in hearts can be through IP₃ and Ca²⁺-calmodulin dependent mechanism.