Mechanisms of intrinsic force in small human airways

Mark E. Wylam, Ailing Xue, Gary C. Sieck

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

We quantified the magnitude and investigated mechanisms regulating intrinsic force (IF) in human airway smooth muscle (hASM). IF was identified by reducing extracellular calcium (Ca 2+) 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 -5M) and is epithelial independent, (2) IF can also be revealed by β-adrenergic activation (isoproterenol), non-specific cationic channel blockade (La 3+) or L-type voltage gated Ca 2+ channel blockade (nifedipine), (3) atropine, indomethacin, AA-861, or pyrilamine did not affect IF, (4) IF was reduced by the intracellular Ca 2+ ([Ca 2+] i) chelating agent BAPTA-AM, (5) ω-conotoxin had no effect on IF. In studies in cultured hASM cells nominally zero Ca 2+ buffer and BAPTA-AM reduced [Ca 2+] i but isoproterenol and nifedipine did not. Taken together these results indicate that rapid reduction of [Ca 2+] i reveals a permissive relationship between extracellular Ca 2+, [Ca 2+] i and IF. However IF can be dissipated by mechanisms effecting Ca 2+ 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.

Original languageEnglish (US)
Pages (from-to)99-108
Number of pages10
JournalRespiratory Physiology and Neurobiology
Volume181
Issue number1
DOIs
StatePublished - Apr 15 2012

Keywords

  • Airway smooth muscle
  • Asthma
  • Human
  • Intracellular calcium concentration [Ca ]
  • Intrinsic force

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

Fingerprint Dive into the research topics of 'Mechanisms of intrinsic force in small human airways'. Together they form a unique fingerprint.

  • Cite this