Chloride Channels

In addition to the GABAa and glycine receptors described previously, the chloride channels include the CLC family, CFTR, and other channel families that have yet to be identified. Chloride channels are involved in the regulation of cell volume, the transport of Cl_, pH homeostasis, and membrane excitability. The CLC channels contain numerous hydrophobic stretches; however, the membrane topology of the CLC channels is unknown, with various models having 8-12 transmembrane segments.

The CFTR is a chloride channel that was cloned from molecular genetic studies of patients with cystic fibrosis. Its major role is in the transport of Cl_ across epithelial cells in many organs, such as the pancreas, lung, sweat glands, and kidneys. CFTR is a member of the ATP-binding cassette (ABC) family of ion transporters. ABC proteins are generally known for mediating the ATP-driven transport of substances; for example, the MDR protein pumps chemotherapeutic drugs out of the cell. Therefore, the CFTR ion channel is a unique member of this family.

Ion channels are fantastic molecular machines. Their functions are fundamental—they act as valves for ions to move into or out of the cell—and thus they play important roles in many physiological processes. The study of ion channels is challenging but rewarding since it ranges from exploring the function of ion channels on the cellular and systems level down to the atomic level to investigating how ion channels as proteins work. The first crystal structures of ion channels have ushered in a new era in ion channel research. With more structures and functional studies of ion channels and the cloning of ion channels involved in channelopathies, the next decade promises to be an exciting time for ion channel research.

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