Chloride channels are a family of anion-selective channels involved in a diverse range of biological processes including the regulation of the excitability of neurons, skeletal, cardiac and smooth muscle, cell volume regulation, transepithelial salt transport, the acidification of intra- and extracellular compartments.
There are five main subtypes of chloride channels:
- Voltage-sensitive ClC channels - a family of 9 (ClC-1-7, ClC-Ka and ClC-Kb), each containing two independently-gated pores that are important for repolarization and stabilization of membrane potentials.
- Ca2+-activated chloride channels (CaCCs) - widely expressed in both excitable and non-excitable cells, activated by intracellular Ca2+ and modulated by CaMKII and calcineurin
- High (maxi) conductance chloride channels - found in skeletal and cardiac muscle cells, neurons, glia, lymphocytes, epithelial cells and placental cells, with a suggested role in cell volume regulation and apoptosis
- Volume-regulated chloride channels (VRACs) - have a role in the regulation of volume decrease of cells in response to swelling. Also regulate membrane excitability, transcellular Cl- transport, angiogenesis, cell proliferation and apoptosis.
- The cystic fibrosis transmembrane conductance regulator (CFTR) - a cAMP-regulated epithelial cell channel involved in fluid transport. Inhibits ENaC, CaCC and VRAC channels and activates ORCC and ROMK2 channels. Homozygous Δ508 mutation causes impaired CFTR trafficking and leads to cystic fibrosis
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