{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T22:21:22Z","timestamp":1769206882226,"version":"3.49.0"},"reference-count":0,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1997,8,1]]},"abstract":"<jats:p> We investigated the muscarinic activation of Ca(2+)-activated Cl- currents [ICl(Ca)] in voltage-clamped equine tracheal myocytes. The threshold of cytosolic free Ca2+ concentration ([Ca2+]i) required for activation of ICl(Ca) was 202 +\/- 22 nM, and full activation of the current occurred at 771 +\/- 31 nM. Hexahydro-sila-difenidol (M3 antagonist) inhibited the methacholine-induced phasic [Ca2+]i increase and ICl(Ca) in a concentration-dependent manner, whereas methoctramine (M2 antagonist) only slightly attenuated the [Ca2+]i increase and ICl(Ca) (14.8 and 21.4%, respectively), consistent with incomplete selectivity. Dialysis of heparin (10 mg\/ml) blocked methacholine-induced [Ca2+]i and ICl(Ca) but had no effect on the caffeine-induced Ca2+ release or ICl(Ca); inositol 1,4,5-trisphosphate (100 microM) induced ICl(Ca) and blocked the methacholine current. Conversely, ruthenium red (50 microM) prevented the caffeine-induced [Ca2+]i release and ICl(Ca) but had no effect on methacholine-induced [Ca2+]i or current. Intracellular dialysis of the calmodulin antagonist N-(6-aminohexyl)-1-naphthalenesulfonamide (W-7, 500 microM) or the Ca2+\/calmodulin-dependent protein kinase inhibitor KN93 (5 microM) had no effect on the [Ca2+]i increase or ICl(Ca). Pertussis toxin (0.5 mg\/ml) did not affect the increase in [Ca2+]i or ICl(Ca). Dialysis with antibodies directed against the alpha-subunit of Gq\/G11 (Gq alpha\/ G alpha 11) blocked the methacholine-induced ICl(Ca) in a concentration-dependent manner, whereas anti-G alpha i-1\/G alpha 1-2 antibodies (1:35) and anti-G alpha i-3\/G(o) alpha antibodies (1:35) were without effect. The results indicate that stimulation of phospholipase C via M3\/Gq proteins is the predominant signaling pathway for the activation of ICl(Ca); at high agonist concentrations, Ca(2+)-induced Ca2+ release does not appear to play a prominent role in muscarinic signaling. <\/jats:p>","DOI":"10.1152\/ajpcell.1997.273.2.c509","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T16:07:55Z","timestamp":1514131675000},"page":"C509-C519","source":"Crossref","is-referenced-by-count":42,"title":["Muscarinic signaling pathway for calcium release and calcium-activated chloride current in smooth muscle"],"prefix":"10.1152","volume":"273","author":[{"given":"Y. X.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6046, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. I.","family":"Kotlikoff","sequence":"additional","affiliation":[{"name":"Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6046, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.1997.273.2.C509","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:32:10Z","timestamp":1718652730000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.1997.273.2.C509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,8,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1997,8,1]]}},"alternative-id":["10.1152\/ajpcell.1997.273.2.C509"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.1997.273.2.c509","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,8,1]]}}}