기니픽 심장과 심근 세포에서 α<SUB>1</SUB>-Adrenergic 자극에 의한 Mg<SUP>2&#8290;</SUP> 유리조절

Regulation of Mg<SUP>2&#8290;</SUP> Release in Guinea Pig Heart and Isolated Ventricular Myocytes by &#1345;<SUB>1</SUB>-Adrenergic Stimulation

<P> Mg<SUP>2&#8290;</SUP> 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 Mg<SUP>2&#8290;</SUP> in mammalian cells is not fully understood. More recently, however, the mechanism of Mg<SUP>2&#8290;</SUP> mobilization by hormonal stimulation has been investigated in hearts and in myocytes. In this work we have investigated the regulation mechanism responsible for the Mg<SUP>2&#8290;</SUP> mobilization induced by α<SUB>1</SUB>-adrenoceptor stimulation in perfused guinea pig hearts or isolated myocytes. The Mg<SUP>2&#8290;</SUP> content of the perfusate or the supernatant was measured by atomic absorbance spectrophotometry. <P> The elimination of Mg<SUP>2&#8290;</SUP> in the medium increased the force of contraction of right ventricular papillary muscles. Phenylephrine also enhanced the force of contraction in the presence of Mg<SUP>2&#8290;</SUP>-free medium. α<SUB>1</SUB>-Agonists such as phenylephrine were found to induce Mg<SUP>2&#8290;</SUP> efflux in both perfused hearts or myocytes. This was blocked by prazosin, a α<SUB>1</SUB>-adrenoceptor antagonist. Mg<SUP>2&#8290;</SUP> efflux by phenylephrine was amplified by Na<SUP>&#8290;</SUP> channel blockers, an increase in extracellular Ca<SUP>2&#8290;</SUP> or a decrease in extracellular Na<SUP>&#8290;</SUP>. By contrast, the Mg<SUP>2&#8290;</SUP> influx was induced by verapamil, nifedipine, ryanodine, lidocaine or tetrodotoxin in perfused hearts, but not in myocytes. W<SUB>7</SUB>, a Ca<SUP>2&#8290;</SUP>/calmodulin antagonist, completely blocked the pheylephrine-, A23187-, veratridine-, Ca<SUP>2&#8290;</SUP>-induced Mg<SUP>2&#8290;</SUP> efflux in perfused hearts or isolated myocytes. In addition, Mg<SUP>2&#8290;</SUP> efflux was induced by W<SUB>7</SUB> in myocytes but not in perfused heart. <P> In conclusion, An increase in Mg<SUP>2&#8290;</SUP> efflux by α<SUB>1</SUB>-adrenoceptor stimulation in hearts can be through IP<SUB>3</SUB> and Ca<SUP>2&#8290;</SUP>-calmodulin dependent mechanism.