Regulation of intracellular calcium in human esophageal smooth muscles.
We have investigated sources of Ca2+ contributing to excitation of human esophageal smooth muscle, using fura 2 to study cytosolic free Ca2+ concentration ([Ca2+]i) in dispersed cells and contraction of intact muscles. Acetylcholine (ACh) caused an initial peak rise of [Ca2+]i followed by a plateau accompanied by reversible contraction. Removal of extracellular Ca2+ or addition of dihydropyridine Ca2+ channel blockers reduced the plateau phase but did not prevent contraction. Caffeine also caused elevation of [Ca2+]i and blocked responses to ACh. Undershoots of [Ca2+]i were apparent after ACh or caffeine. Blockade of the sarcoplasmic reticular Ca(2+)-ATPase by cyclopiazonic acid (CPA) reduced the ACh-evoked increase of [Ca2+]i and abolished the undershoot, indicating involvement of Ca2+ stores. When contraction was studied in intact muscles, removal of Ca2+ or addition of nifedipine reduced, but did not abolish, carbachol (CCh)-induced contraction. Elevation of extracellular K+ caused contraction that was inhibited by nifedipine, although CCh still elicited contraction. CPA caused contraction and suppressed the CCh-induced contraction, whereas ryanodine reduced CCh-induced contraction. Our studies provide evidence that muscarinic excitation of human esophagus involves both release of Ca2+ from intracellular stores and influx of Ca2+.
Sims
S M
SM
Department of Physiology, University of Western Ontario, London, Canada.
Jiao
Y
Y
Preiksaitis
H G
HG
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000378:metabolism; D004947:Esophagus / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000201:enzymology
D004791:Enzyme Inhibitors; D007211:Indoles; D002110:Caffeine; D004533:Egtazic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium; C000543:cyclopiazonic acid