Mechanisms of intrinsic force in small human airways.
We quantified the magnitude and investigated mechanisms regulating intrinsic force (IF) in human airway smooth muscle (hASM). IF was identified by reducing extracellular calcium (Ca2+) concentration to nominally zero in freshly isolated isometrically mounted 2mm human bronchi. Our results show: (1) the magnitude of IF is ∼50% of the maximal total force elicited by acetylcholine (10(-5) M) and is epithelial independent, (2) IF can also be revealed by β-adrenergic activation (isoproterenol), non-specific cationic channel blockade (La3+) or L-type voltage gated Ca2+ channel blockade (nifedipine), (3) atropine, indomethacin, AA-861, or pyrilamine did not affect IF, (4) IF was reduced by the intracellular Ca2+ ([Ca2+]i) chelating agent BAPTA-AM, (5) ω-conotoxin had no effect on IF. In studies in cultured hASM cells nominally zero Ca2+ buffer and BAPTA-AM reduced [Ca2+]i but isoproterenol and nifedipine did not. Taken together these results indicate that rapid reduction of [Ca2+]i reveals a permissive relationship between extracellular Ca2+, [Ca2+]i and IF. However IF can be dissipated by mechanisms effecting Ca2+ sensitivity. We speculate that an increase of IF, a fundamental property of ASM, could be related to human airway clinical hyperresponsiveness and must be accounted for in in vitro studies of hASM.
Division of Pulmonary and Critical Care Medicine, Departments of Medicine, Pediatrics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. wylam.mark@mayo.edu
Mark E
ME
Wylam
Ailing
A
Xue
Gary C
GC
Sieck
D000109:Acetylcholine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D018679:Cholinergic Agonists; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium