These channels may conduct many different ions, but are named for chloride because its concentration in vivo is much higher than other anions.

Voltage-gated chloride channels perform numerous crucial physiological and cellular functions, such as controlling pH, volume homeostasis, transporting organic solutes, regulating cell migration, proliferation, and differentiation.

CLCN1 is involved in setting and restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney.

Chloride channels are also important for maintaining safe ion concentrations within plant cells.

[3] Each subunit consists of two related halves oriented in opposite directions, forming an 'antiparallel' structure.

Researchers have suggested that this mutual repulsion contributes to the high rate of conduction through the pore.

[5] Though the precise function of these domains is not fully characterized, their importance is illustrated by the pathologies resulting from their mutation.

Particular CLC transporters and proteins have modulated activity when bound with ATP, ADP, AMP, or adenosine at the CBS domains.

Single-channel patch-clamp studies demonstrated this biophysical property even before the dual-pore structure of CLC channels had been resolved.

Each fast gate opens independently of the other and the ion conductance measured during these studies reflects a binomial distribution.

The common gate is also affected by the bonding of adenosine nucleotides to the intracellular CBS domains.

[3] The CLC exchangers are localized to intracellular components like endosomes or lysosomes and help regulate the pH of their compartments.

[8] The first member of this family to be characterized was a respiratory epithelium, Ca2+-regulated, chloride channel protein isolated from bovine tracheal apical membranes.

The purified complex, when reconstituted in a planar lipid bilayer, behaved as an anion-selective channel.

Distant homologues may be present in plants, ciliates and bacteria, Synechocystis and Escherichia coli, so at least some domains within E-ClC family proteins have an ancient origin.

The Chloride Intracellular Ion Channel (CLIC) Family (TC# 1.A.12) consists of six conserved proteins in humans (CLIC1, CLIC2, CLIC3, CLIC4, CLIC5, CLIC6).

These proteins are thought to function in the regulation of the membrane potential and in transepithelial ion absorption and secretion in the kidney.

The bovine p64 protein is 437 amino acyl residues in length and has the two putative TMSs at positions 223-239 and 367-385.

Structural studies showed that in the soluble form, CLIC proteins adopt a GST fold with an active site exhibiting a conserved glutaredoxin monothiol motif, similar to the omega class GSTs.

Any of these mutations can prevent the proper folding of the protein and induce its subsequent degradation, resulting in decreased numbers of chloride channels in the body.