CFTR is a chloride channel whose gating process involves coordinated interactions among the regulatory (R) domain and the nucleotide-binding folds (NBFs). Protein kinase A phosphorylation of serine residues renders the R domain from inhibitory to stimulatory and enables ATP binding and hydrolysis at the NBFs, which in turn control opening and closing of the chloride channel.

Chloride channels play an essential role in a variety of physiological functions and in human diseases. Historically, the field of chloride channels has long been neglected owing to the lack of powerful selective pharmacological agents that are needed to overcome the technical challenge of characterizing the molecular identities of these channels. Recently, members of the LRRC8 family have been...

CLC proteins are found in cells from prokaryotes to mammals and perform functions in plasma membranes and intracellular vesicles. Several genetic human diseases and mouse models underscore their broad physiological functions in mammals. These functions range from the control of excitability to transepithelial transport, endocytotic trafficking and acidification of synaptic vesicles. The recent ...

With the sequencing of the human genome it turned out that many of the genetically identified genes have an unknown function and one of the major problems of biology is the “annotation” of the genome. But the reverse problem persists, i.e., that for many functionally well-defined proteins the coding gene has not been identified. This reverse problem is difficult to tackle because the molecular ...

Plasma membrane Cl- channels perform a variety of functions, including control of excitability in neurons and muscle, cell volume regulation and transepithelial transport. Structurally, three classes of Cl- channels have been identified: ligand-gated, postsynaptic Cl- channels (e.g. GABA and glycine receptors); the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels (which b...

Voltage-gated anion channels are present in almost every living cell and have many physiological functions. Recently, a novel gene family encoding voltage-gated chloride channels, the ClC family, was identified. The knowledge of primary amino acid sequences has allowed for the study of these anion channels in heterologous expression systems and made possible the combination of site-directed mut...

Taurine, a major osmolyte of vertebrate hearts, is released from the skate heart at increased rates during hypotonic stress. We tested the hypothesis that this taurine release is mediated by chloride channels activated by swelling. Two inhibitors of the channels, NPPB and DIDS, inhibited the volume-activated release of taurine from embryonic skate hearts. These results support the hypothesis th...

We have characterized the conduction and blocking properties of two different chloride channels from brain mitochondrial inner membranes after incorporation into planar lipid bilayers. Our experiments revealed the existence of channels with a mean conductance of 158 ± 7 and 301 ± 8 pS in asymmetrical 200 mM cis/50 mM trans KCl solutions. We determined that the channels were ten times more perme...

ClC-0 is a chloride channel whose gating is sensitive to voltage, chloride, and pH. In a previous publication, we showed that the K149C mutation causes a +70-mV shift in the voltage dependence of ClC-0 fast gating. In this paper we analyze the effects of a series of mutations at K149 on the voltage and chloride dependence of gating. By fitting our data to the previously proposed four-state mode...