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Comparison of the gating behaviour of human and murine cystic fibrosis transmembrane conductance regulator Cl − channels expressed in mammalian cells
Author(s) -
Lansdell K. A.,
Delaney S. J.,
Lunn D. P.,
Thomson S. A.,
Sheppard D. N.,
Wainwright B. J.
Publication year - 1998
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 - 10.1111/j.1469-7793.1998.379bq.x
Subject(s) - cystic fibrosis transmembrane conductance regulator , cystic fibrosis , gating , chinese hamster ovary cell , chemistry , microbiology and biotechnology , intracellular , chloride channel , biophysics , biology , biochemistry , genetics , receptor
1 To investigate the function of the murine cystic fibrosis transmembrane conductance regulator (CFTR), a full‐length cDNA encoding wild‐type murine CFTR was assembled and stably expressed in Chinese hamster ovary (CHO) cells. 2 Like human CFTR, murine CFTR formed Cl − channels that were regulated by cAMP‐dependent phosphorylation and intracellular ATP. However, murine CFTR Cl − channels had a reduced single‐channel conductance and decreased open probability ( P o ) compared with those of human CFTR. 3 Analysis of the dwell time distributions of single channels suggested that the reduced P o of murine CFTR was caused by both decreased residence in the open state and transitions to a new closed state, described by an intermediate closed time constant. 4 For both human and murine CFTR, ATP and ADP regulated the rate of exit from the long‐lived closed state. 5 5′‐Adenylylimidodiphosphate (AMP‐PNP) and pyrophosphate, two compounds that disrupt cycles of ATP hydrolysis, stabilized the open state of human CFTR. However, neither agent locked murine CFTR Cl − channels open, although AMP‐PNP increased the P o of murine CFTR. 6 The data indicate that although human and murine CFTR have many properties in common, some important differences in function are observed. These differences could be exploited in future studies to provide new understanding about CFTR.