Characterization of cAMP dependent CFTR-chloride channels in human tracheal gland cells

• Published in: FEBS letters Vol. 321; no. 1; pp. 73 - 78
• Main Authors: BECQ, F, MERTEN, M. D, VOELCKEL, M. A, GOLA, M, FIGARELLA, C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 19-04-1993
• Subjects: Base Sequence; Biological and medical sciences; Cell physiology; cells; channels; chloride; cyclic AMP; Cyclic AMP - metabolism; cystic fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; dependent; Electric Conductivity; Fundamental and applied biological sciences. Psychology; Gene Expression; Humans; In Vitro Techniques; man; Membrane and intracellular transports; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular and cellular biology; Molecular Sequence Data; Oligodeoxyribonucleotides - chemistry; RNA, Messenger - genetics; trachea; Trachea - anatomy & histology; Trachea - chemistry; Trachea - metabolism; Human; Transmembrane protein; Cell culture; Chlorides; Ionic conductivity; Homology; Patch clamp method; Ionic channel; Tracheal gland
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(93)80624-4

Human tracheal gland cells are believed to be a major site at the origin of cystic fibrosis. Since this disease is due to mutations in a protein called CFTR, we looked for the activity of CFTR in human tracheal gland cells in culture. We have identified CFTR-like chloride-selective channels as having a linear current voltage relationship and unitary conductance of 7 pS in these cells. In cell-attached patches, theophylline (1 mM), IBMX (1 mM), or a cocktail of dibutyryl cAMP (1 mM) and IBMX (0.1 mM) promoted the opening of channels. The unitary current had a reversal potential close to the cell resting potential. Replacement of choline by K+ or Na+ in the pipette solution was without effect on the current-voltage relationship, the reversal potential or the unitary conductance, which is consistent with the chloride selectivity of the channel. Channels were always found clustered and their opening probability was not noticeably dependent on membrane potential. This work therefore represents the first observation of a CFTR-like channel activity in submucosal gland cells.