Effect of inotropic stimulation on cytosolic Mg2+ in isolated rat heart: a 31P magnetic resonance study.
Alterations in cytosolic metabolites and [Mg2+]i were monitored using 31P magnetic resonance spectroscopy during inotropic stimulation of isolated rat heart [10 nM isoproterenol, 0.6 microM isobutyl-1-methylxanthine (IBMX), 5 microM ouabain]. All drugs significantly elevated contractile function (rate-pressure product) and MVO2 by approximately 100-150% (P less than 0.001), decreased cytosolic [creatine phosphate] ([CrP]) and [ATP] (approximately 65 and 80% of control values, respectively) (P less than 0.001), increased [Pi] to more than 180% of pretreatment values, and decreased [H+] by less than 15% (P less than 0.05). A significant relative shift in the alpha-P and beta-P resonances of ATP (P less than 0.01) occurred with inotropic stimulation. [Mg2+]i calculated on the basis of these shifts was found to be 0.78 +/- 0.1 mM in control hearts, and increased to maxima of 1.9 +/- 0.2, 2.0 +/- 0.2, and 2.9 +/- 0.2 mM during infusion of isoproterenol, IBMX, and ouabain, respectively. Changes in [Mg2+]i correlate with cytosolic [ATP] + [CrP] in all hearts (r = 0.89, 0.91, and 0.88 in isoproterenol-, IBMX-, and ouabain-treated hearts, respectively). The significantly higher [Mg2+]i with ouabain infusion (P less than 0.01) at similar workloads and [ATP] + [CrP] supports the proposal that a ouabain-inhibited Mg2+ pump exists in the plasma membrane. The data support acute changes in [Mg2+]i during alterations in inotropic state that may be important in modulating metabolic and contractile function.
Headrick
J P
JP
Division of Science and Technology, Griffith University, Queensland, Australia.
Willis
R J
RJ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D011919:Rats, Inbred Strains
D002316:Cardiotonic Agents; D010710:Phosphates; D010758:Phosphorus; D010042:Ouabain; D008274:Magnesium; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine