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Acetylcholine Ca2+ stores refilling directly involves a dihydropyridine-sensitive channel in dog trachea
J P Bourreau1, A P Abela, C Y Kwan
1Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
The American Journal of Physiology
|September 1, 1991
Summary
Smooth muscle calcium (Ca2+) stores are depleted by repeated acetylcholine stimulation. Refilling these stores involves two pathways: one using the sarcoplasmic reticulum Ca2+ pump and another using extracellular Ca2+ influx via L-type Ca2+ channels.
Area of Science:
- Pharmacology
- Cell Physiology
- Smooth Muscle Biology
Background:
- Intracellular Ca2+ stores are crucial for regulating smooth muscle contraction.
- Acetylcholine (ACh) stimulates smooth muscle via intracellular Ca2+ release.
- Nifedipine, a calcium channel blocker, affects smooth muscle contractility.
Purpose of the Study:
- To investigate the mechanisms of refilling agonist-sensitive intracellular Ca2+ stores in smooth muscle.
- To determine the roles of extracellular Ca2+ influx and sarcoplasmic reticulum (SR) Ca2+ pump in store refilling.
- To elucidate the involvement of L-type Ca2+ channels and SR Ca2+ release channels in Ca2+ homeostasis.
Main Methods:
- Repetitive acetylcholine stimulation of smooth muscle in the presence of nifedipine.
- Measurement of developed tension and intracellular Ca2+ store content.
- Experiments in Ca(2+)-free and Ca(2+)-containing media with various agents (nifedipine, BAY K 8644, cyclopiazonic acid, ryanodine).
Main Results:
- Repeated ACh stimulation depleted agonist-sensitive Ca2+ stores, reducing muscle tension.
- Store refilling at rest required extracellular Ca2+, was inhibited by nifedipine, and enhanced by BAY K 8644.
- During ACh stimulation, refilling was inhibited by nifedipine and cyclopiazonic acid (CPA) but potentiated by BAY K 8644; BAY K 8644 reversed CPA's inhibition.
Conclusions:
- Two distinct pathways refill ACh-sensitive Ca2+ stores: one via CPA-sensitive SR Ca2+-ATPase and another via CPA-insensitive dihydropyridine-sensitive Ca2+ influx.
- Extracellular Ca2+ influx through L-type Ca2+ channels and SR Ca2+ release channels are involved in plasmalemma-SR Ca2+ transport.
- Nifedipine impairs store refilling, while BAY K 8644 enhances it, suggesting a role for L-type Ca2+ channels in regulating intracellular Ca2+ dynamics.