Acetylcholine-induced calcium signaling and contraction of airway smooth muscle cells in lung slices
dc.contributor.author | Bergner, Albrecht | |
dc.contributor.author | Sanderson, Michael J. | |
dc.date | 2022-08-11T08:09:30.000 | |
dc.date.accessioned | 2022-08-23T16:33:47Z | |
dc.date.available | 2022-08-23T16:33:47Z | |
dc.date.issued | 2002-01-30 | |
dc.date.submitted | 2008-10-31 | |
dc.identifier.citation | J Gen Physiol. 2002 Feb;119(2):187-98. | |
dc.identifier.issn | 0022-1295 (Print) | |
dc.identifier.pmid | 11815668 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/38183 | |
dc.description.abstract | The Ca(2+) signaling and contractility of airway smooth muscle cells (SMCs) were investigated with confocal microscopy in murine lung slices (approximately 75-microm thick) that maintained the in situ organization of the airways and the contractility of the SMCs for at least 5 d. 10--500 nM acetylcholine (ACH) induced a contraction of the airway lumen and a transient increase in [Ca(2+)](i) in individual SMCs that subsequently declined to initiate multiple intracellular Ca(2+) oscillations. These Ca(2+) oscillations spread as Ca(2+) waves through the SMCs at approximately 48 microm/s. The magnitude of the airway contraction, the initial Ca(2+) transient, and the frequency of the subsequent Ca(2+) oscillations were all concentration-dependent. In a Ca(2+)-free solution, ACH induced a similar Ca(2+) response, except that the Ca(2+) oscillations ceased after 1--1.5 min. Incubation with thapsigargin, xestospongin, or ryanodine inhibited the ACH-induced Ca(2+) signaling. A comparison of airway contraction with the ACH-induced Ca(2+) response of the SMCs revealed that the onset of airway contraction correlated with the initial Ca(2+) transient, and that sustained airway contraction correlated with the occurrence of the Ca(2+) oscillations. Buffering intracellular Ca(2+) with BAPTA prohibited Ca(2+) signaling and airway contraction, indicating a Ca(2+)-dependent pathway. Cessation of the Ca(2+) oscillations, induced by ACH-esterase, halothane, or the absence of extracellular Ca(2+) resulted in a relaxation of the airway. The concentration dependence of the airway contraction matched the concentration dependence of the increased frequency of the Ca(2+) oscillations. These results indicate that Ca(2+) oscillations, induced by ACH in murine bronchial SMCs, are generated by Ca(2+) release from the SR involving IP(3)- and ryanodine receptors, and are required to maintain airway contraction. | |
dc.language.iso | en_US | |
dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=11815668&dopt=Abstract">Link to Article in PubMed</a> | |
dc.subject | Acetylcholine | |
dc.subject | Animals | |
dc.subject | Calcium Signaling | |
dc.subject | Dose-Response Relationship, Drug | |
dc.subject | Lung | |
dc.subject | Male | |
dc.subject | Mice | |
dc.subject | Mice, Inbred BALB C | |
dc.subject | Muscle Contraction | |
dc.subject | Muscle, Smooth | |
dc.subject | Physiology | |
dc.title | Acetylcholine-induced calcium signaling and contraction of airway smooth muscle cells in lung slices | |
dc.type | Journal Article | |
dc.source.journaltitle | The Journal of general physiology | |
dc.source.volume | 119 | |
dc.source.issue | 2 | |
dc.identifier.legacyfulltext | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2063&context=oapubs&unstamped=1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/oapubs/1064 | |
dc.identifier.contextkey | 659253 | |
refterms.dateFOA | 2022-08-23T16:33:47Z | |
html.description.abstract | <p>The Ca(2+) signaling and contractility of airway smooth muscle cells (SMCs) were investigated with confocal microscopy in murine lung slices (approximately 75-microm thick) that maintained the in situ organization of the airways and the contractility of the SMCs for at least 5 d. 10--500 nM acetylcholine (ACH) induced a contraction of the airway lumen and a transient increase in [Ca(2+)](i) in individual SMCs that subsequently declined to initiate multiple intracellular Ca(2+) oscillations. These Ca(2+) oscillations spread as Ca(2+) waves through the SMCs at approximately 48 microm/s. The magnitude of the airway contraction, the initial Ca(2+) transient, and the frequency of the subsequent Ca(2+) oscillations were all concentration-dependent. In a Ca(2+)-free solution, ACH induced a similar Ca(2+) response, except that the Ca(2+) oscillations ceased after 1--1.5 min. Incubation with thapsigargin, xestospongin, or ryanodine inhibited the ACH-induced Ca(2+) signaling. A comparison of airway contraction with the ACH-induced Ca(2+) response of the SMCs revealed that the onset of airway contraction correlated with the initial Ca(2+) transient, and that sustained airway contraction correlated with the occurrence of the Ca(2+) oscillations. Buffering intracellular Ca(2+) with BAPTA prohibited Ca(2+) signaling and airway contraction, indicating a Ca(2+)-dependent pathway. Cessation of the Ca(2+) oscillations, induced by ACH-esterase, halothane, or the absence of extracellular Ca(2+) resulted in a relaxation of the airway. The concentration dependence of the airway contraction matched the concentration dependence of the increased frequency of the Ca(2+) oscillations. These results indicate that Ca(2+) oscillations, induced by ACH in murine bronchial SMCs, are generated by Ca(2+) release from the SR involving IP(3)- and ryanodine receptors, and are required to maintain airway contraction.</p> | |
dc.identifier.submissionpath | oapubs/1064 | |
dc.contributor.department | Department of Physiology | |
dc.source.pages | 187-98 |