Chloride Channels

Abstract

Chloride channels are integral membrane proteins that regulate the movement of chloride ions across cellular membranes. They perform a vital role in physiological processes such as epithelial transport, the regulation of nerve and muscle cell membrane excitability, cell volume regulation and in determining the pH within cytoplasmic membrane‐bound organelles. Several distinct protein families form chloride channels whose opening is regulated by different stimuli including neurotransmitter binding, changes in the concentrations of intracellular second messengers including cAMP and Ca 2+ , and phosphorylation. High‐resolution protein structures of many types of chloride channels have been solved by x‐ray crystallography and cryo‐electron microscopy. Mutations in genes encoding chloride channels impair their function and cause a variety of genetic diseases. Several clinically useful medicines act by modulating the activity of specific types of chloride channels. Key Concepts Chloride channels are ion channels that facilitate the movement of chloride ions across cell membranes. Chloride channels play fundamental roles in diverse physiological processes. Several distinct gene families encode proteins that function as chloride channels and have unique atomic structures. Genetic diseases result due to mutations in chloride channels that impair their function. The mechanism of action of a number of drugs used clinically involves chloride channels as specific targets.