Regulation of Magnesium Release by cAMP during Chemical Hypoxia in the Rat Heart and Isolated Ventricular Myocytes
Regulation of Magnesium Release by cAMP during Chemical Hypoxia in the Rat Heart and Isolated Ventricular Myocytes
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제3권 제1호
- : SCOPUS, SCIE, KCI등재
- 1999.01
- 59 - 68 (10 pages)
<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.