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Disulphonic stilbene block of cystic fibrosis transmembrane conductance regulator Cl‐ channels expressed in a mammalian cell line and its regulation by a critical pore residue.
Author(s) -
Linsdell P,
Hanrahan J W
Publication year - 1996
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1996.sp021719
Subject(s) - dids , cystic fibrosis transmembrane conductance regulator , biophysics , chemistry , membrane potential , extracellular , biochemistry , microbiology and biotechnology , membrane , biology , gene
1. The disulphonic stilbenes 4,4'‐dinitrostilbene‐2,2'‐disulphonic acid (DNDS) and 4,4'‐diisothiocyanostilbene‐2,2'‐disulphonic acid (DIDS) were shown to cause a voltage‐dependent inhibition of macroscopic cystic fibrosis transmembrane conductance regulator (CFTR) Cl‐ currents expressed in baby hamster kidney cells when applied to the cytoplasmic face of the membrane. These compounds are known to be relatively ineffective at blocking CFTR from the extracellular side of the membrane. 2. Mutation of a positively charged arginine, previously suggested to be located in the channel pore (R347), to a negatively charged aspartate significantly reduced the affinity of block by both DNDS and DIDS, suggesting that this residue contributes to the binding site for disulphonic stilbenes. 3. It is suggested that the CFTR Cl‐ channel may contain a relatively large inner vestibule in which a number of large anions bind and block Cl‐ permeation. Arginine 347 may be involved in anion binding within this region.