Regulation of magnesium release by cAMP during chemical hypoxia in the rat heart and isolated ventricular myocytes.
- Author:
Jin Shang KIM
1
;
Antonio SCARPA
Author Information
1. Department of Pharmacology, Chonbuk National University Veterinary Medicine, Chonju, 561-756 South Korea.
- Publication Type:Original Article
- Keywords:
Magnesium;
cAMP;
ATP;
Heart;
Ventricular myocytes;
Chemical hypoxia
- MeSH:
Adenosine Triphosphate;
Animals;
Anoxia*;
Heart*;
Imipramine;
Magnesium*;
Muscle Cells*;
Norepinephrine;
Perfusion;
Quinidine;
Rats*;
Spectrophotometry
- From:The Korean Journal of Physiology and Pharmacology
1999;3(1):59-68
- CountryRepublic of Korea
- Language:English
-
Abstract:
Chemically induced hypoxia has been shown to induce a depletion of ATP. Since intracellular free Mg2+ ((Mg2+)i) appears to be tightly regulated following cellular energy depletion, we hypothesized that the increase in (Mg2+)i would result in Mg2+ extrusion following hormonal stimulation. To determine the relation between Mg2+ efflux and cellular energy state in a hypoxic rat heart and isolated myocytes, (Mg2+)i, ATP and Mg2+ content were measured by using mag-fura-2, luciferin-luciferase and atomic absorbance spectrophotometry. Mg2+ effluxes were stimulated by norepinephrine (NE) or cAMP analogues, respectively. Mg2+ 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 (Mg2+)i confirmed that ATP depletion was accompanied by an increase in (Mg2+)i. No change in Mg2+ efflux was observed when cells were incubated with MI. In the presence of MI, the cAMP-induced Mg2+ effluxes were inhibited by quinidine, imipramine, and removal of extracellular Na+. In addition, after several min of perfusion with Na+-free buffer, a large increase in Mg2+ efflux occurred when Na+-free buffer was switched to 120 mM Na+ containing buffer. A similar Mg2+ efflux was observed in myocytes. These effluxes were inhibited by quinidine and imipramine. These results indicate that the activation of Mg2+ effluxes by hormonal stimulation is directly dependent on intracellular Mg2+ contents and that these Mg2+ effluxes appear to occur through the Na+-dependent Na+/Mg2+ exchange system during chemical hypoxia.
