TRANSMEMBRANE MUTATIONS ALTER THE CHANNEL CHARACTERISTICS OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR EXPRESSED IN XENOPUS-OOCYTES

We report that Xenopus oocytes injected with wild-type cystic fibrosis transmembrane regulator (CFTR) RNA exhibit cAMP-regulated Cl- currents. Injection of CFTR RNA bearing R117H, a mutation associated with mild disease, induces cAMP-regulated Cl- currents. The magnitudes of the currents induced by R117H were consistently lower than those induced by expression of wild-type CFTR. Western blotting with anti-CFTR antibody confirms that protein was expressed in oocytes injected with either normal or the mutant form of CFTR mRNA. The rank order of single channel open channel probabilities of wild-type and mutant CFTR Cl- channels is wild-type > R117H. These data demonstrate that mutations in the transmembrane region affect CFTR channel properties and are consistent with the hypothesis that CF disease severity may be correlated with reduced cAMP-regulated Cl- conductances of mutant CFTR.