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Calcium-Activated Chloride Channels

  • George Gallos
  • Charles W. EmalaSr.Email author
Chapter

Abstract

Emerging functional evidence demonstrates the importance of membrane potential in the regulation of many intracellular signaling processes. The efflux of chloride through the plasma membrane has been identified as a major contributor to plasma membrane depolarization in airway smooth muscle. Early studies demonstrated that calcium arising from intracellular sources and released by ryanodine or IP3 receptor activation on the sarcoplasmic-reticulum-induced plasma membrane chloride currents. Moreover, external calcium entry through voltage-dependent calcium channels was shown to augment calcium-activated chloride currents. One of the earliest studies in this area suggested a role for chloride influencing uptake and release of calcium from the sarcoplasmic reticulum in addition to chloride flux’s effect on plasma membrane electrical potential. Recently the elusive proteins responsible for calcium-activated chloride currents in many cells (TMEM16/anoctamin family) were cloned, which has renewed interest in the field of calcium-activated chloride channels (CaCCs). Anoctamin 1 has been identified on the apical side of airway epithelium, is critical to fluid secretion, and has been associated with increased mucin secretion in asthmatics. Anoctamin 1 is critical to the development of the trachea as global knockout mice exhibit severe tracheomalacia. Anoctamin 1 has been immunochemically localized to airway smooth muscle and human bronchi were shown to contract less effectively in the presence of benzbromarone, an antagonist of these channels. Studies of the TMEM16/anoctamin family of CaCCs are revolutionizing the understanding of calcium-activated chloride currents in many cell types, and emerging evidence suggests that this channel also contributes to the regulation of airway smooth muscle tone.

Keywords

TMEM16/Anoctamin Electrophysiology Niflumic acid Benzbromarone Membrane potential Sarcoplasmic reticulum 

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of AnesthesiologyColumbia UniversityNew YorkUSA

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