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.