Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2847350 | Respiratory Physiology & Neurobiology | 2012 | 10 Pages |
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 2 mm 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.
► Intrinsic force generation is a fundamental property of human airway smooth muscle. ► Intrinsic force can be identified by reducing extracellular calcium concentration in isolated isometrically mounted 2 mm human bronchi. ► The magnitude of intrinsic force is ∼50% of maximal acetylcholine elicited force. ► There is a permissive relationship between extracellular Ca2+, [Ca2+]i and IF.