Chloride channel (CLC) family is a functionally and structurally diverse group of anion-selective channels which participate in cellular processes, such as the regulation of excitability of skeletal, neurons, cardiac and smooth muscle, transepithelial salt transport, cell volume regulation, cell cycle and apoptosis, and the acidification of internal and extracellular compartments. Except for the transmitter-gated GABA and glycine receptors, the well-characterized CLCs can be divided into certain members of the voltage-sensitive subfamily, calcium-activated channel, high-conductance channel, volume-regulated channel, and the cystic fibrosis transmembrane conductance regulator (CFTR). CLCs show the permeability sequence at physiological pH as Cl- > Br- > I-. The expression of the Cl- transporter is regulated both temporally and spatially so that the rest of the intracellular Cl- is dynamically modulated. Dramatic changes in intracellular Cl- have been documented to occur both slowly during development and more acutely in response to synaptic activity.
Here shows part of CLC members in humans in the chart. The CLC family contains 10-12 transmembrane helices and each protein has the ability to form a single pore. The mammalian CLC family consists of nine members that fall into three subfamilies. Among them, CLCN1 is implicated in setting and restoring the resting membrane potential of skeletal muscle, while others play important roles in the solute concentration mechanism for the kidney.
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