Low extracellular Mg2+ contraction of arterial muscle: role of protein kinase C and protein tyrosine phosphorylation.

The effects of extracellular Mg2+ ion ([Mg2+]0) deficiency on basal tension of isolated rat aortae and rat aortic smooth muscle cell Ca2+ metabolism were investigated in the present study. The contractions of rat aortae induced by diverse concentrations of low [Mg2+]0 were potentiated, greatly, by removal of the endothelium or pre-incubation of intact rat aortic rings with L-N(G)-monomethyl-arginine (L-NMMA). [Mg2+]0 deficiency-induced contractions were inhibited, to different degrees, by pre-treatment of the vessels with low concentrations of Gö6976, bisindolymaleimide I, genistein or a combination of bisindolymaleimide I with genistein. IC50 levels found for these three agents were found to be not too different from Ki values for these drugs. Pre-treatment of rat aortic smooth muscle cells with Gö6976, bisindolymaleimide I, genistein or a combination of bisindolymaleimide I with genistein suppressed, significantly, or almost eliminated both the rapid and stable increments in [Ca2+]i induced by Mg2+-free medium. The present findings suggest that both protein kinase C and protein tyrosine phosphorylation appear to play important roles in Mg2+ deficiency-induced contractions of isolated rat aortic smooth muscle, most likely via phosphorylation of L-type Ca2+ channels.