TMEM16A/ANO1 channels contribute to the myogenic response in cerebral arteries

Simon Bulley, Zachary P. Neeb, Sarah K. Burris, John P. Bannister, Candice M. Thomas-Gatewood, Wanchana Jangsangthong, Jonathan Jaggar

Research output: Contribution to journalArticle

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Abstract

Rationale: Pressure-induced arterial depolarization and constriction (the myogenic response) is a smooth muscle cell (myocyte)-specific mechanism that controls regional organ blood flow and systemic blood pressure. Several different nonselective cation channels contribute to pressure-induced depolarization, but signaling mechanisms involved are unclear. Similarly uncertain is the contribution of anion channels to the myogenic response and physiological functions and mechanisms of regulation of recently discovered transmembrane 16A (TMEM16A), also termed Anoctamin 1, chloride (Cl) channels in arterial myocytes. Objective:: To investigate the hypothesis that myocyte TMEM16A channels control membrane potential and contractility and contribute to the myogenic response in cerebral arteries. Methods and Results: Cell swelling induced by hyposmotic bath solution stimulated Cl currents in arterial myocytes that were blocked by TMEM16A channel inhibitory antibodies, RNAi-mediated selective TMEM16A channel knockdown, removal of extracellular calcium (Ca), replacement of intracellular EGTA with BAPTA, a fast Ca chelator, and Gd and SKF-96365, nonselective cation channel blockers. In contrast, nimodipine, a voltage-dependent Ca channel inhibitor, or thapsigargin, which depletes intracellular Ca stores, did not alter swelling-activated TMEM16A currents. Pressure-induced (-40 mm Hg) membrane stretch activated ion channels in arterial myocyte cell-attached patches that were inhibited by TMEM16A antibodies and were of similar amplitude to recombinant TMEM16A channels. TMEM16A knockdown reduced intravascular pressure-induced depolarization and vasoconstriction but did not alter depolarization-induced (60 mmol/L K) vasoconstriction. Conclusions:: Membrane stretch activates arterial myocyte TMEM16A channels, leading to membrane depolarization and vasoconstriction. Data also provide a mechanism by which a local Ca signal generated by nonselective cation channels stimulates TMEM16A channels to induce myogenic constriction.

Original languageEnglish (US)
Pages (from-to)1027-1036
Number of pages10
JournalCirculation research
Volume111
Issue number8
DOIs
StatePublished - Sep 1 2012

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Cerebral Arteries
Muscle Cells
Vasoconstriction
Cations
1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
Calcium
Pressure
Constriction
Smooth Muscle Myocytes
Membranes
Nimodipine
Chloride Channels
Thapsigargin
Antibodies
Egtazic Acid
Regional Blood Flow
Calcium Channels
RNA Interference
Baths
Ion Channels

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Bulley, S., Neeb, Z. P., Burris, S. K., Bannister, J. P., Thomas-Gatewood, C. M., Jangsangthong, W., & Jaggar, J. (2012). TMEM16A/ANO1 channels contribute to the myogenic response in cerebral arteries. Circulation research, 111(8), 1027-1036. https://doi.org/10.1161/CIRCRESAHA.112.277145

TMEM16A/ANO1 channels contribute to the myogenic response in cerebral arteries. / Bulley, Simon; Neeb, Zachary P.; Burris, Sarah K.; Bannister, John P.; Thomas-Gatewood, Candice M.; Jangsangthong, Wanchana; Jaggar, Jonathan.

In: Circulation research, Vol. 111, No. 8, 01.09.2012, p. 1027-1036.

Research output: Contribution to journalArticle

Bulley, S, Neeb, ZP, Burris, SK, Bannister, JP, Thomas-Gatewood, CM, Jangsangthong, W & Jaggar, J 2012, 'TMEM16A/ANO1 channels contribute to the myogenic response in cerebral arteries', Circulation research, vol. 111, no. 8, pp. 1027-1036. https://doi.org/10.1161/CIRCRESAHA.112.277145
Bulley S, Neeb ZP, Burris SK, Bannister JP, Thomas-Gatewood CM, Jangsangthong W et al. TMEM16A/ANO1 channels contribute to the myogenic response in cerebral arteries. Circulation research. 2012 Sep 1;111(8):1027-1036. https://doi.org/10.1161/CIRCRESAHA.112.277145
Bulley, Simon ; Neeb, Zachary P. ; Burris, Sarah K. ; Bannister, John P. ; Thomas-Gatewood, Candice M. ; Jangsangthong, Wanchana ; Jaggar, Jonathan. / TMEM16A/ANO1 channels contribute to the myogenic response in cerebral arteries. In: Circulation research. 2012 ; Vol. 111, No. 8. pp. 1027-1036.
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AU - Bulley, Simon

AU - Neeb, Zachary P.

AU - Burris, Sarah K.

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AU - Thomas-Gatewood, Candice M.

AU - Jangsangthong, Wanchana

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