HYPERGLYCEMIA ALTERS CYTOPLASMIC CA2-MUSCLE CELLS( RESPONSES TO CAPACITATIVE CA2+ INFLUX IN RAT AORTIC SMOOTH)

Concentrations of free cytoplasmic Ca2+ in rat aortic smooth muscle (R ASM) cells were monitored using the ratiometric Ca2+ indicator furs 2- acetoxymethyl ester (AM). In RASM cells cultured in 5 mM Glc, incubati on with angiotensin II, ATP, or thapsigargin [a selective inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase] depleted SR Ca2+ stores and initiated a capacitative Ca2+ influx through the plasma membrane. This influx was resistant to verapamil, a selective inhibitor of L-typ e voltage-gated Ca2+ channels, but was sensitive to SKF-96365, an inhi bitor of the receptor-operated Ca2+ entry pathway. RASM cells cultured in 25 mM Glc exhibited a significant decrease in cytoplasmic Ca2+ res ponses to agonist-induced Ca2+ release from SE stores and to subsequen t capacitative Ca2+ entry. In addition, the cytoplasmic response to th apsigargin-induced release of Ca2+ from the SE in hyperglycemic cells peaked more sharply than in control cells and returned to baseline mor e rapidly. The effects of hyperglycemia were not overcome by myo-inosi tol supplementation.