NA-DEPENDENT REGULATION OF INTRACELLULAR FREE MAGNESIUM CONCENTRATIONIN ISOLATED RAT VENTRICULAR MYOCYTES

Changes in ionized intracellular free magnesium concentration [Mg2+](i ) were measured in isolated, superfused rat ventricular myocytes using mag-fura-2. Cells were superfused with media containing high or low M g concentrations ([Mg](0)), with and without Na (Na-0) and/or Ca (Ca-0 ). Increasing [Mg](0) from 1 to 5 mmol/l in Ca-free solutions had no s ignificant effect on [Mg2+](i) when [Na](0) was normal. However, [Mg2](i) rose steadily when Na-0 was completely replaced by either tetrame thylammonium (TMA) or K. This [Mg2+](i) rise was inhibited by imiprami ne (10 mu mol/l) but not by verapamil (25 mu mol/l). [Mg2+](i) returne d rapidly from a high to its initial level on superfusing cells with b asic medium containing normal Ca, Na and Mg. [Mg2+](i) recovery requir ed Na-0 and was inhibited by imipramine (10 mu mol/l). When Mg-0 was r emoved from Ca-free superfusates, the [Mg2+](i) decreased whether or n ot Na-0 was present. However, [Mg2+](i) decreased most when Na-0 was r eplaced by K. Neither imipramine nor verapamil affected the magnitude of this fall, but verapamil slowed it. [Mg2+](i) rapidly increased to normal when depleted cells were superfused with basic medium with or w ithout Ca-0. Both imipramine and verapamil slowed this recovery. Super fusion of cells with Ca-free media containing strophanthidin (20 mu mo l/l) caused [Mg2+](i) to rise, but only if the medium contained Mg (1 mmol/l). The data suggest that Mg can enter cardiac myocytes through r outes which close when physiological [Mg2+](i) is attained. One pathwa y for Mg flux is by a Na-dependent, imipramine-sensitive mechanism whi ch is probably a Na-Mg antiport. (C) 1996 Academic Press Limited