Na-dependent regulation of intracellular free magnesium concentration in 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 Mg concentrations ([Mg]o), with and without Na (Nao) and/or Ca (Cao). Increasing [Mg]o from 1 to 5 mmol/l in Ca-free solutions had no significant effect on [Mg2+]i when [Na]o was normal. However, [Mg2+]i rose steadily when Nao was completely replaced by either tetramethylammonium (TMA) or K. This [Mg2+]i rise was inhibited by imipramine (10 mumol/l) but not by verapamil (25 mumol/l). [Mg2+]i returned rapidly from a high to its initial level on superfusing cells with basic medium containing normal Ca, Na and Mg. [Mg2+]i recovery required Nao and was inhibited by imipramine (10 mumol/l). When Mgo was removed from Ca-free superfusates, the [Mg2+]i decreased whether or not Nao was present. However, [Mg2+]i decreased most when Nao was replaced 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 without Cao. Both imipramine and verapamil slowed this recovery. Superfusion of cells with Ca-free media containing strophanthidin (20 mumol/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 routes which close when physiological [Mg2+]i is attained. One pathway for Mg flux is by a Na-dependent, imipramine-sensitive mechanism which is probably a Na-Mg antiport.
Handy
R D
RD
Department of Physiology, University Medical School, Edinburgh, UK.
Gow
I F
IF
Ellis
D
D
Flatman
P W
PW
D000818:Animals; D017920:Antiporters / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012964:Sodium / Q000378:metabolism*; D013223:Statistics as Topic; D013327:Strophanthidin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D017920:Antiporters; D007473:Ion Channels; C046250:sodium-magnesium antiporter; D013327:Strophanthidin; D012964:Sodium; D014700:Verapamil; D008274:Magnesium; D007099:Imipramine