Abstract: | We have investigated sources ofCa2+ contributing to excitation ofhuman esophageal smooth muscle, using fura 2 to study cytosolic freeCa2+ concentration(Ca2+]i)in dispersed cells and contraction of intact muscles. Acetylcholine (ACh) caused an initial peak rise ofCa2+]ifollowed by a plateau accompanied by reversible contraction. Removal ofextracellular Ca2+ or addition ofdihydropyridine Ca2+ channelblockers reduced the plateau phase but did not prevent contraction.Caffeine also caused elevation ofCa2+]iand blocked responses to ACh. Undershoots ofCa2+]iwere apparent after ACh or caffeine. Blockade of the sarcoplasmic reticular Ca2+-ATPase bycyclopiazonic acid (CPA) reduced the ACh-evoked increase ofCa2+]iand abolished the undershoot, indicating involvement ofCa2+ stores. When contraction wasstudied in intact muscles, removal ofCa2+ or addition of nifedipinereduced, but did not abolish, carbachol (CCh)-induced contraction.Elevation of extracellular K+caused contraction that was inhibited by nifedipine, although CCh stillelicited contraction. CPA caused contraction and suppressed theCCh-induced contraction, whereas ryanodine reduced CCh-induced contraction. Our studies provide evidence that muscarinic excitation ofhuman esophagus involves both release ofCa2+ from intracellular stores andinflux of Ca2+. |