Skip to main content
Journal cover image

Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction.

Publication ,  Journal Article
Huang, F; Zhang, H; Wu, M; Yang, H; Kudo, M; Peters, CJ; Woodruff, PG; Solberg, OD; Donne, ML; Huang, X; Sheppard, D; Fahy, JV; Wolters, PJ ...
Published in: Proc Natl Acad Sci U S A
October 2, 2012

Mucous cell hyperplasia and airway smooth muscle (ASM) hyperresponsiveness are hallmark features of inflammatory airway diseases, including asthma. Here, we show that the recently identified calcium-activated chloride channel (CaCC) TMEM16A is expressed in the adult airway surface epithelium and ASM. The epithelial expression is increased in asthmatics, particularly in secretory cells. Based on this and the proposed functions of CaCC, we hypothesized that TMEM16A inhibitors would negatively regulate both epithelial mucin secretion and ASM contraction. We used a high-throughput screen to identify small-molecule blockers of TMEM16A-CaCC channels. We show that inhibition of TMEM16A-CaCC significantly impairs mucus secretion in primary human airway surface epithelial cells. Furthermore, inhibition of TMEM16A-CaCC significantly reduces mouse and human ASM contraction in response to cholinergic agonists. TMEM16A-CaCC blockers, including those identified here, may positively impact multiple causes of asthma symptoms.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

October 2, 2012

Volume

109

Issue

40

Start / End Page

16354 / 16359

Location

United States

Related Subject Headings

  • Respiratory System
  • Muscle, Smooth
  • Muscle Contraction
  • Mucins
  • Microscopy, Fluorescence
  • Mice
  • Immunohistochemistry
  • Humans
  • Epithelial Cells
  • Chloride Channels
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Huang, F., Zhang, H., Wu, M., Yang, H., Kudo, M., Peters, C. J., … Rock, J. R. (2012). Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction. Proc Natl Acad Sci U S A, 109(40), 16354–16359. https://doi.org/10.1073/pnas.1214596109
Huang, Fen, Hongkang Zhang, Meng Wu, Huanghe Yang, Makoto Kudo, Christian J. Peters, Prescott G. Woodruff, et al. “Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction.Proc Natl Acad Sci U S A 109, no. 40 (October 2, 2012): 16354–59. https://doi.org/10.1073/pnas.1214596109.
Huang F, Zhang H, Wu M, Yang H, Kudo M, Peters CJ, et al. Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16354–9.
Huang, Fen, et al. “Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction.Proc Natl Acad Sci U S A, vol. 109, no. 40, Oct. 2012, pp. 16354–59. Pubmed, doi:10.1073/pnas.1214596109.
Huang F, Zhang H, Wu M, Yang H, Kudo M, Peters CJ, Woodruff PG, Solberg OD, Donne ML, Huang X, Sheppard D, Fahy JV, Wolters PJ, Hogan BLM, Finkbeiner WE, Li M, Jan Y-N, Jan LY, Rock JR. Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16354–16359.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

October 2, 2012

Volume

109

Issue

40

Start / End Page

16354 / 16359

Location

United States

Related Subject Headings

  • Respiratory System
  • Muscle, Smooth
  • Muscle Contraction
  • Mucins
  • Microscopy, Fluorescence
  • Mice
  • Immunohistochemistry
  • Humans
  • Epithelial Cells
  • Chloride Channels