EXTRACELLULAR MG2-MUSCLE CELLS( INHIBITS CAPACITATIVE CA2+ ENTRY IN VASCULAR SMOOTH)

Background Agonist-induced Ca2+ entry is thought to be mediated by cap acitative Ca2+ entry other than L-type Ca2+ channels in vascular smoot h muscle cells (VSMCs). The mechanism for capacitative Ca2+ entry has not been fully elucidated. Our objective was to examine the effect of external Mg2+ on capacitative Ca2+ entry in cultured rat aortic VSMCs. Methods and Results Three doses of external Mg2+ concentration (nomin ally 0, 1, and 5 mmol/L) were used. After exposure to 1 mu mol/L angio tensin II (Ang II) in Ca2+-free medium, addition of Ca2+ to the medium caused an increase in cytosolic free Ca2+ concentration ([Ca2+](i)), indicating Ang II-induced Ca2+ influx. This Ca2+ influx was attenuated in cells preincubated with high external Mg2+ concentrations or with 1 mu mol/L nifedipine. After VSMCs in Ca2+-free medium were exposed to 1 mu mol/L thapsigargin, which inhibits the sarcoplasmic reticulum Ca 2+-ATPase and depletes Ca2+ stores, addition of Ca2+ to the medium ind uced an increase in [Ca2+](i), indicating capacitative Ca2+ entry. Thi s entry pathway was found to be independent of dihydropyridine-sensiti ve Ca2+ channels and inhibited by increased external Mg2+ concentratio n. External Mg2+ concentration did not influence Ca2+ efflux across th e plasma membrane after stimulation with Ang II plus thapsigargin. Con clusions Results suggest that in VSMCs, capacitative Ca2+ entry is red uced by external Mg2+. This mechanism may explain in part the inhibito ry effect of external Mg2+ on Ca2+ handling.