Acetylcholine Ca2+ stores refilling directly involves a dihydropyridine-sensitive channel in dog trachea

• Published in: The American journal of physiology Vol. 261; no. 3 Pt 1; p. C497
• Main Authors: Bourreau, J P, Abela, A P, Kwan, C Y, Daniel, E E
• Format: Journal Article
• Language: English
• Published: United States 01.09.1991
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Acetylcholine - pharmacology; Animals; Calcium - metabolism; Calcium - pharmacology; Calcium Channels - drug effects; Calcium Channels - physiology; Dogs; Egtazic Acid - pharmacology; Female; In Vitro Techniques; Kinetics; Male; Membrane Potentials - drug effects; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Nifedipine - pharmacology; Ryanodine - pharmacology; Trachea - drug effects; Trachea - physiology
• ISSN: 0002-9513
• DOI: 10.1152/ajpcell.1991.261.3.c497

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).