CA2+ ENTRY ACTIVATED BY EMPTYING OF INTRACELLULAR CA2+ STORES IN ILEAL SMOOTH-MUSCLE OF THE RAT

1 The effects of depletion of intracellular Ca2+ stores on muscle tension and the intracellular Ca2+ concentration ([Ca2+])(i) were studied in fura-2 loaded longitudinal smooth muscle cells of the rat ileum. 2 After exposure to a Ca2+-free solution, application of Ca2+ caused a small contraction and a rise in [Ca2+](i), both of which were potentiated when the muscle was challenged with carbachol or caffeine before the addition of Ca2+. 3 Cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic reticulum Ca2+-ATPase, dose-dependently decreased tension development and the rises in [Ca2+](i) induced by carbachol and caffeine in the Ca2+-free solution, but conversely increased the Ca2+-induced responses even in the presence of the voltage-dependent Ca2+ channel blockers, methoxyverapamil and nifedipine. 4 The contraction and rise in [Ca2+](i) evoked by Ca2+ gradually declined with time after removal of CPA, while the reverse was the case for the responses to carbachol and caffeine. 5 The Ca2+-induced contraction and rise in [Ca2+](i) in the presence of CPA were inhibited by the replacement of Na+ with K+ or Cs+, and by the addition of Cd2+, Ba2+, Ni2+ or La3+. 6 The influx of Mn2+ was much greater in extent in the presence of CPA than in its absence. 7 These results suggest that the emptying of intracellular Ca2+ stores may activate Ca2+ influx not associated with voltage-dependent Ca2+ channels in the rat ileal smooth muscle.