Caveolae and propofol effects on airway smooth muscle

K. J. Grim, A. J. Abcejo, A. Barnes, V. Sathish, D. F. Smelter, G. C. Ford, M. A. Thompson, Y. S. Prakash, C. M. Pabelick

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background. The i.v. anaesthetic propofol produces bronchodilatation. Airway relaxation involves reduced intracellular Ca2+ ([Ca 2+]i) in airway smooth muscle (ASM) and lipid rafts (caveolae), and constitutional caveolin proteins regulate [Ca2+]i. We postulated that propofol-induced bronchodilatation involves caveolar disruption. Methods. Caveolar fractions of human ASM cells were tested for propofol content. [Ca 2+]i responses of ASM cells loaded with fura-2 were performed in the presence of 10 M histamine with and without clinically relevant concentrations of propofol (10 and 30 μM and intralipid control). Effects on sarcoplasmic reticulum (SR) Ca2+ release were evaluated in zero extracellular Ca2+ using the blockers Xestospongin C and ryanodine. Store-operated Ca2+ entry (SOCE) after SR depletion was evaluated using established techniques. The role of caveolin-1 in the effect of propofol was tested using small interference RNA (siRNA) suppression. Changes in intracellular signalling cascades relevant to [Ca2+]i and force regulation were also evaluated. Results. Propofol was present in ASM caveolar fractions in substantial concentrations. Exposure to 10 or 30 M propofol form decreased [Ca2+]i peak (but not plateau) responses to histamine by ∼40, an effect persistent in zero extracellular Ca2. Propofol effects were absent in caveolin-1 siRNA-transfected cells. Inhibition of ryanodine receptors prevented propofol effects on [Ca2+]i, while propofol blunted [Ca2+]i responses to caffeine. Propofol reduced SOCE, an effect also prevented by caveolin-1 siRNA. Propofol effects were associated with decreased caveolin-1 expression and extracellular signal-regulated kinase phosphorylation. Conclusions. These novel data suggest a role for caveolae (specifically caveolin-1) in propofol-induced bronchodilatation. Due to its lipid nature, propofol may transiently disrupt caveolar regulation, thus altering ASM [Ca 2+]i.

Original languageEnglish (US)
Pages (from-to)444-453
Number of pages10
JournalBritish journal of anaesthesia
Volume109
Issue number3
DOIs
StatePublished - Sep 2012

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Keywords

  • bronchial smooth muscle
  • bronchodilatation
  • calcium regulation
  • caveolin
  • intravenous anaesthetic
  • signalling

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Grim, K. J., Abcejo, A. J., Barnes, A., Sathish, V., Smelter, D. F., Ford, G. C., Thompson, M. A., Prakash, Y. S., & Pabelick, C. M. (2012). Caveolae and propofol effects on airway smooth muscle. British journal of anaesthesia, 109(3), 444-453. https://doi.org/10.1093/bja/aes130