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A change in gating mode leading to increased intrinsic Cl- channel activity compensates for defective processing in a cystic fibrosis mutant corresponding to a mild form of the disease.

1995; Springer Nature; Volume: 14; Issue: 11 Linguagem: Inglês

10.1002/j.1460-2075.1995.tb07239.x

1460-2075

Guy Champigny, Jean‐Luc Imler, Édith Puchelle, Wilfried Dalemans, Valentin K. Gribkoff, J. Hinnrasky, Karin Dott, Pascal Barbry, Andréa Pavirani, Michel Lazdunski,

Biosensors and Analytical Detection

Research Article1 June 1995free access A change in gating mode leading to increased intrinsic Cl- channel activity compensates for defective processing in a cystic fibrosis mutant corresponding to a mild form of the disease. G. Champigny G. Champigny Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author J.L. Imler J.L. Imler Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author E. Puchelle E. Puchelle Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author W. Dalemans W. Dalemans Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author V. Gribkoff V. Gribkoff Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author J. Hinnrasky J. Hinnrasky Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author K. Dott K. Dott Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author P. Barbry P. Barbry Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author A. Pavirani A. Pavirani Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author M. Lazdunski M. Lazdunski Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author G. Champigny G. Champigny Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author J.L. Imler J.L. Imler Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author E. Puchelle E. Puchelle Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author W. Dalemans W. Dalemans Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author V. Gribkoff V. Gribkoff Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author J. Hinnrasky J. Hinnrasky Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author K. Dott K. Dott Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author P. Barbry P. Barbry Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author A. Pavirani A. Pavirani Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author M. Lazdunski M. Lazdunski Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. Search for more papers by this author Author Information G. Champigny1, J.L. Imler1, E. Puchelle1, W. Dalemans1, V. Gribkoff1, J. Hinnrasky1, K. Dott1, P. Barbry1, A. Pavirani1 and M. Lazdunski1 1Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne. The EMBO Journal (1995)14:2417-2423https://doi.org/10.1002/j.1460-2075.1995.tb07239.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info The effects of the mild cystic fibrosis (CF) mutation P574H were analysed and compared with those of three severe ones (delta I507, delta F508 and R560T). Immunochemical and functional analyses indicate that the rank order of CFTR expression at the cell surface is: wild type CFTR > P574H >> delta F508 >> R560T approximately 0. Patch-clamp analysis indicates that the open probability of P574H Cl- channels is almost twice as high as that of the wild type CFTR-Cl- channel. This increased intrinsic activity of individual P574H CFTR-Cl- channels compensates for the lower number of P574H CFTR-Cl- channels reaching the cell surface, and probably explains the milder form of CF associated with the P574H mutation. NS004, a recently described activator, restores near normal CFTR activity in cells expressing the P574H-CFTR channel. The P574H mutation modifies the gating mode of the channel with a large increase (approximately x 7) in the mean channel open time. Proline 574 might play an important role in the process connecting ATP hydrolysis at the nucleotide binding domain and opening and closing events of the CFTR-Cl- channel. Previous ArticleNext Article Volume 14Issue 111 June 1995In this issue RelatedDetailsLoading ...