WS06.2 R117H-CFTR has a defect in channel gating activity that can be potentiated by ivacaftor

The magnitude of ivacaftor effects on fluid secretion via R117H-CFTR channels: Human in vivo measurements

We optically measured effects of orally available ivacaftor (Kalydeco®) on sweat rates of identified glands in 3 R117H subjects, each having a unique set of additional mutations, and compared them with 5 healthy control subjects tested contemporaneously. We injected β-adrenergic agonists intradermally to stimulate CFTR-dependent 'C-sweat' and methacholine to stimulate 'M-sweat', which persists ...

Ivacaftor potentiation of multiple CFTR channels with gating mutations.

BACKGROUND The investigational CFTR potentiator ivacaftor (VX-770) increased CFTR channel activity and improved lung function in subjects with CF who have the G551D CFTR gating mutation. The aim of this in vitro study was to determine whether ivacaftor potentiates mutant CFTR with gating defects caused by other CFTR gating mutations. METHODS The effects of ivacaftor on CFTR channel open proba...

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...

Title: Synergistic Potentiation of CFTR gating by two chemically distinct potentiators, Ivacaftor (VX-770) and NPPB

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...