Physiological and pharmacological characterization of the N1303K mutant CFTR.

ABSTRACT:

Background

N1303K, one of the common, severe disease-causing mutations in the CFTR gene, causes both defective biogenesis and gating abnormalities of the CFTR protein. The goals of the present study are to quantitatively assess the gating defects associated with the N1303K mutation and its pharmacological response to CFTR modulators including potentiators VX-770 and GLPG1837 and correctors VX-809, and VX-661.

Methods

Gating behavior and pharmacological responses to CFTR potentiators were assessed using patch-clamp technique in the excised, inside-out mode. We also examined the effects of GLPG1837, VX-770, VX-809 and VX-661 on N1303K-CFTR surface expression using Western blot analysis.

Results

Like wild-type (WT) CFTR, N1303K-CFTR channels were activated by protein kin

SUBMITTER: DeStefano S 

PROVIDER: S-EPMC7008954 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature