Altered channel gating mechanism for CFTR inhibition by a high-affinity thiazolidinone blocker

Cftr Channel Gating

Two papers, one in this issue (Weinreich et al., 1999) and the other in the April issue of The Journal (Zelt-wanger et al., 1999), help clarify the gating mechanisms of cystic fibrosis transmembrane conductance regulator (CFTR) Cl Ϫ channels, the products of the gene found mutated in cystic fibrosis patients. CFTR is a most unusual ion channel. It is a prominent member of the ABC transporter su...

A kinase-regulated mechanism controls CFTR channel gating by disrupting bivalent PDZ domain interactions.

Dynamic regulation of ion channels is critical for maintaining fluid balance in epithelial tissues. Cystic fibrosis, a genetic disease characterized by impaired fluid transport in epithelial tissues, is caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel activity. Recent studies have shown that binding of PSD-95/Dlg/ZO-1 (PDZ) domain proteins to CFTR i...

Control of CFTR channel gating by phosphorylation and nucleotide hydrolysis.

Control of CTFR Channel Gating by Phosphorylation and Nucleotide Hydrolysis. Physiol. Rev. 79, Suppl.: S77-S107, 1999. - The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel is the protein product of the gene defective in cystic fibrosis, the most common lethal genetic disease among Caucasians. Unlike any other known ion channel, CFTR belongs to the ATP-binding cassette su...

ATP-independent CFTR channel gating and allosteric modulation by phosphorylation.

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) channel, an ATP binding cassette (ABC) transporter. CFTR gating is linked to ATP binding and dimerization of its two nucleotide binding domains (NBDs). Channel activation also requires phosphorylation of the R domain by poorly understood mechanisms. Unlike conventional ligand-gated chan...

hERG potassium channel inhibition by ivabradine requires channel gating.