Cellular Mg++ accumulation is altered by extracellular Na+ and directly affects agonist-induced mobilization of Ca++ in vascular smooth muscle

Effects of altered Na+, Ca++ and Mg++ concentrations on 45Ca and 28Mg distribution and binding as well as of changes in cellular Mg++ on mobilization of Ca++ by added norepinephrine (NE) were examined in the rabbit aortic media-intimal layer. Uptake of 45Ca at cellular high affinity sites was decreased by Mg++ much more than 28Mg uptake was altered by Ca++. Substitution of Na+ affects 45Ca uptake primarily at extracellular (La( )-accessible) binding sites. Muscles were pre-loaded with Mg++ by incubation in a low-Na+ solution (75% Na+ replaced isosmotically with sucrose) for 30 min followed by a 90 min exposure to a similar solution also containing 15 mM MgCl2. These tissues, upon examination in normal (154 mM) Na(+)-containing solution, indicated decreased retention of that cellular, high-affinity Ca++ fraction important for NE-induced contractile response. Accordingly, release of 45Ca from this site and associated tension responses to added NE were attenuated in these muscles. These results suggest that variations in extracellular Na+ concentration modulate binding and subsequent mobilization of activator Ca++ by agonists through alterations in cellular Mg++ content in vascular smooth muscle.