A CHLORIDE CHANNEL WIDELY EXPRESSED IN EPITHELIAL AND NONEPITHELIAL CELLS

CHLORIDE channels have several functions, including the regulation of cell volume 1,2 stabilizing membrane potential 3,4, signal transduction 5,6 and transepithelial transport 7. The plasma membrane Cl- channels already cloned belong to different structural classes: ligand-gated channels 5,6, voltage-gated channels 8,9, and possibly transporters of the ATP-binding-cassette type (if the cystic fibrosis transmembrane regulator 10 is a Cl- channel 11-13). The importance of chloride channels is illustrated by the phenotypes that can result from their malfunction: cystic fibrosis, in which transepithelial transport is impaired, and myotonia 3, in which ClC-1, the principal skeletal muscle Cl- channel, is defective 9. Here we report the properties of ClC-2, a new member of the voltage-gated Cl- channel family. Its sequence is approximately 50% identical to either the Torpedo electroplax Cl- channel, ClC-0 (ref. 8), or the rat muscle Cl- channel, ClC-1 (ref. 9). Isolated initially from rat heart and brain, it is also expressed in pancreas, lung and liver, for example, and in pure cell lines of fibroblastic, neuronal, and epithelial origin, including tissues and cells affected by cystic fibrosis. Expression in Xenopus oocytes induces Cl- currents that activate slowly upon hyperpolarization and display a linear instantaneous current-voltage relationship. The conductivity sequence is Cl- greater-than-or-equal-to Br- > I-. The presence of ClC-2 in such different cell types contrasts with the highly specialized expression of ClC-1 (ref. 9) and also with the cloned cation channels, and suggests that its function is important for most cells.