title: Relationship between asynchronous Ca2+ waves and force development in intact smooth muscle bundles of the porcine trachea.
abstract: Fluctuations in intracellular calcium concentration ([Ca2+]i) constitute the main link in excitation-contraction coupling (E-C coupling) in airway smooth muscle cells (ASMC). It has recently been reported that ACh induces asynchronous recurring Ca2+ waves in intact ASMC of murine bronchioles. With the use of a novel technique allowing us to simultaneously measure subcellular [Ca2+]i and force generation in ASMC located within an intact tracheal muscle bundle, we examined a similar pattern of Ca2+ signaling in the trachea. We found that application of ACh resulted in the generation of recurring intracellular Ca2+ waves progressing along the longitudinal axis of the ribbon-shaped intact ASMC. These Ca2+ waves were not synchronized between neighboring cells, and induction of wave-like [Ca2+]i oscillations was temporally associated with development of force by the tracheal muscle bundle. By comparing the concentration dependence of force generation and the parameters characterizing the [Ca2+]i oscillations, we found that the concentration-dependent increase in ACh-induced force development by the tracheal smooth muscle bundle is achieved by differential recruitment of intact ASMC to initiate Ca2+ waves and by enhancement in the frequency of [Ca2+]i oscillations and elevation of interspike [Ca2+]i once the cells are recruited. Our findings demonstrate that asynchronous recurring Ca2+ waves underlie E-C coupling in ACh-induced contraction of the intact tracheal smooth muscle bundle. Furthermore, in contrast to what was reported in enzymatically dissociated ASMC, Ca2+ influx through the L-type voltage-gated Ca2+ channel was not an obligatory requirement for the generation of [Ca2+]i oscillations and development of force in ACh-stimulated intact ASMC.
authors.affiliation: St. Paul's Hospital, The iCAPTURE Center, University of British Columbia, Vancouver, British Columbia V6Z 1Y6, Canada.
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Kuo
authors.forename: Jiazhen
authors.initials: J
authors.lastname: Dai
authors.forename: Chun Yong
authors.initials: CY
authors.lastname: Seow
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000648:ultrastructure; D013552:Swine; D014132:Trachea / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; D000109:Acetylcholine