Acetylcholine Ca2+ stores refilling directly involves a dihydropyridine-sensitive channel in dog trachea.
Repetitive stimulation of the smooth muscle with acetylcholine (ACh) in the continuous presence of nifedipine resulted in a progressive decrease in the developed tension. This was associated with a decrease in the content of the agonist-sensitive intracellular Ca2+ stores. Agonist-sensitive internal Ca2+ stores appeared to be readily depleted by successive or prolonged agonist stimulation in Ca(2+)-free medium. The refilling of the empty stores when the muscle is at rest required extracellular Ca2+, was decreased by nifedipine, and was increased by BAY K 8644 and by increased external Ca2+ concentration. Refilling of stores during ACh stimulation in Ca(2+)-containing medium was decreased by nifedipine and by cyclopiazonic acid (CPA), an inhibitor of the sarcoplasmic reticulum (SR) Ca2+ pump, and was potentiated by BAY K 8644. BAY K 8644 reversed the inhibitory effect of CPA on stores Ca2+ refilling. Ryanodine in normal Krebs increased muscle resting tension, an effect not observed in Ca(2+)-free medium, blocked by nifedipine and enhanced by BAY K 8644. We propose that the refilling of ACh-sensitive internal Ca2+ stores involves two distinct pathways, one dependent on the uptake of cytosolic Ca2+ via a CPA-sensitive SR Ca(2+)-adenosinetriphosphatase, and the other pathway dependent on extracellular Ca2+ influx via a dihydropyridine-sensitive Ca2+ channel and is CPA insensitive. The refilling pathway between plasmalemma and SR may involve a plasmalemma L-type Ca2+ channel (dihydropyridine sensitive) and the SR Ca2+ release channel (ryanodine sensitive).
Bourreau
J P
JP
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Abela
A P
AP
Kwan
C Y
CY
Daniel
E E
EE
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology*; D012433:Ryanodine / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D012433:Ryanodine; D004533:Egtazic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium