CHARACTERIZATION OF CAMP-DEPENDENT CFTR-CHLORIDE CHANNELS IN HUMAN TRACHEAL GLAND-CELLS

Human tracheal gland cells are believed to be a major site at the orig in of cystic fibrosis. Since this disease is due to mutations in a pro tein called CFTR, we looked for the activity of CFTR in human tracheal gland cells in culture. We have identified CFTR-like chloride-selecti ve channels as having a linear current-voltage relationship and unitar y conductance of 7 pS in these cells. In cell-attached patches, theoph ylline (I mM), IBMX (1 mM), or a cocktail of dibutyryl cAMP (I mM) and IBMX (0.1 mM) promoted the opening of channels. The unitary current h ad a reversal potential close to the cell resting potential. Replaceme nt of choline by K+ or Na+ in the pipette solution was without effect on the current-voltage relationship, the reversal potential or the uni tary conductance, which is consistent with the chloride selectivity of the channel. Channels were always found clustered and their opening p robability was not noticeably dependent on membrane potential. This wo rk therefore represents the first observation of a CFTR-like channel a ctivity in submucosal gland cells.