title: Ionic mechanisms and Ca2+ handling in airway smooth muscle.
abstract: Asthma is a disease characterised by reversible contraction of airway smooth muscle. Many signalling pathways are now known to underlie that contraction, almost all of which revolve around Ca(2+) handling. Ca(2+) homeostasis in turn is governed by a wide variety of ionic mechanisms, which are still poorly understood. The present review will briefly summarise those mechanisms that have been recognised for decades, but will then devote considerable attention to several novel ionic signalling mechanisms such as capacitative Ca(2+) entry, the reverse mode of the Na(+)/Ca(2+) exchanger, the role of Cl(-) channels in the release of internal Ca(2+) and that of ryanodine receptors in the refilling of the sarcoplasmic reticulum, as well as the regulation of the monomeric G-protein Rho by ionic mechanisms. Lastly, evidence will be provided that Ca(2+)-dependent contraction may be driven by spatial and temporal heterogeneities in the intracellular Ca(2+) concentration (i.e. Ca(2+) waves/oscillations) rather than by an increase in the global steady state intracellular Ca(2+) concentration.
authors.affiliation: Asthma Research Group, Firestone Institute for Respiratory Health, St. Joseph's Hospital, Dept of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Hirota
authors.forename: P
authors.initials: P
authors.lastname: Helli
authors.forename: L J
authors.initials: LJ
authors.lastname: Janssen
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007477:Ions / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials; D008954:Models, Biological; D009130:Muscle, Smooth / Q000378:metabolism*; D009991:Oscillometry; D012137:Respiratory System; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D014132:Trachea / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D007477:Ions; D019831:Sodium-Calcium Exchanger; D020741:rho GTP-Binding Proteins; D002118:Calcium