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        Regulation of Magnesium Release by cAMP during Chemical Hypoxia in the Rat Heart and Isolated Ventricular Myocytes

        Jin Shang Kim,Antonio Scarpa 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.1

        <P> Chemically induced hypoxia has been shown to induce a depletion of ATP. Since intracellular free Mg<SUP>2⁢ </SUP>([Mg<SUP>2⁢</SUP>]<SUB>i</SUB>) appears to be tightly regulated following cellular energy depletion, we hypothesized that the increase in [Mg<SUP>2⁢</SUP>]<SUB>i </SUB>would result in Mg<SUP>2⁢ </SUP>extrusion following hormonal stimulation. To determine the relation between Mg<SUP>2⁢</SUP> efflux and cellular energy state in a hypoxic rat heart and isolated myocytes, [Mg<SUP>2</SUP><SUP>⁢</SUP>]<SUB>i</SUB>, ATP and Mg<SUP>2⁢ </SUP>content were measured by using mag-fura-2, luciferin-luciferase and atomic absorbance spectrophotometry. Mg<SUP>2⁢</SUP> effluxes were stimulated by norepinephrine (NE) or cAMP analogues, respectively. Mg<SUP>2⁢</SUP> effluxes induced by NE or cAMP were more stimulated in the presence of metabolic inhibitors (MI). Chemical hypoxia with NaCN (2 mM) caused a rapid decrease of cellular ATP within 1 min. Measurement of [Mg<SUP>2⁢</SUP>]<SUB>i </SUB>confirmed that ATP depletion was accompanied by an increase in [Mg<SUP>2⁢</SUP>]<SUB>i</SUB>. No change in Mg<SUP>2⁢</SUP> efflux was observed when cells were incubated with MI. In the presence of MI, the cAMP-induced Mg<SUP>2⁢</SUP> effluxes were inhibited by quinidine, imipramine, and removal of extracellular Na<SUP>⁢</SUP>. In addition, after several min of perfusion with Na<SUP>⁢</SUP>-free buffer, a large increase in Mg<SUP>2⁢</SUP> efflux occurred when Na<SUP>⁢</SUP>-free buffer was switched to 120 mM Na<SUP>⁢ </SUP>containing buffer. A similar Mg<SUP>2⁢</SUP> efflux was observed in myocytes. These effluxes were inhibited by quinidine and imipramine. These results indicate that the activation of Mg<SUP>2⁢</SUP> effluxes by hormonal stimulation is directly dependent on intracellular Mg<SUP>2⁢</SUP> contents and that these Mg<SUP>2⁢</SUP> effluxes appear to occur through the Na<SUP>⁢</SUP>-dependent Na<SUP>⁢</SUP>/Mg<SUP>2⁢</SUP> exchange system during chemical hypoxia.

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