Calcium-activated chloride channels: Potential targets for antinociceptive therapy

Int J Biochem Cell Biol. 2019 Jun:111:37-41. doi: 10.1016/j.biocel.2019.04.006. Epub 2019 Apr 18.

Abstract

The molecular identity of calcium-activated chloride channels (CaCCs) was clarified only some ten years ago when it was linked to the family of "transmembrane proteins of unknown function 16″ (TMEM16). Since then, numerous studies have been conducted both to define their role in physiology and identify their biophysical functions. For the latter, the ultrastructural description of mouse TMEM16 A was a breakthrough. CaCCs were functionally described in a number of different tissues including first-order sensory neurons. The activating rise in intracellular calcium concentration can be caused by an influx of calcium through other calcium permeable ion channels. Calcium release from intracellular stores, mediated by G-protein coupled receptors, also leads to CaCC activation. Prominent inflammatory mediators like bradykinin or serotonin stimulate CaCCs via such a mechanism. The (patho) physiological function of these ion channels renders them promising targets for antinociceptive treatment.

Keywords: Ca-activated chloride channels; CaCC; Nociception; TMEM16; Therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Anoctamin-1 / chemistry
  • Anoctamin-1 / metabolism
  • Chloride Channels / chemistry
  • Chloride Channels / metabolism*
  • Humans
  • Molecular Targeted Therapy / methods*
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism

Substances

  • Analgesics
  • Anoctamin-1
  • Chloride Channels