title: L-type Ca(2+) channels, Ca(2+)-induced Ca(2+) release, and BK(Ca) channels in airway stretch-induced contraction.
abstract: Resistance arteries constrict in response to mechanical stress. This response is myogenic in nature, and reliant on membrane depolarization, activation of L-type Ca(2+) channels, Ca(2+)-induced Ca(2+)-release and large conductance Ca(2+)-dependent K(+) channels (BK(Ca)). Airway smooth muscle is also affected by mechanical stress: a deep inspiration produces a bronchodilation in healthy individuals, but bronchoconstriction in moderate to severe asthmatics. In this study, our objective was to investigate the regulation of this airway stretch-activated contractile response (R(stretch)), and explore its similarities to the vascular myogenic response. Using a pharmacological approach in intact bovine bronchial segments cannulated horizontally in an organ bath, we showed the ability of carbachol (2-carbamoyloxyethyl-trimethyl-azanium), KCl, neurokinin-A, and U46619 (9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z, 13E-dien-1-oic acid) to generate R(stretch) in a concentration-dependent manner. R(stretch) was significantly reduced by nifedipine, ryanodine, and iberiotoxin, suggesting that it possesses characteristics similar to those of the vascular smooth muscle myogenic response, such as a role for membrane depolarization, L-type Ca(2+) channel, ryanodine receptors and BK(Ca) channel activation. This study demonstrates a novel role for the L-type Ca(2+) channel in airway smooth muscle and provides new insights into possible mechanisms regulating the deep inspiration-induced bronchoconstriction seen in asthmatics.
authors.affiliation: Firestone Institute for Respiratory Health, Father Sean O'Sullivan Research Centre, and Department of Medicine, McMaster University, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Jeremy Mark
authors.initials: JM
authors.lastname: Hernandez
authors.forename: Luke Jeffrey
authors.initials: LJ
authors.lastname: Janssen
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002417:Cattle; D005260:Female; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D019837:Ryanodine Receptor Calcium Release Channel; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium