PHYSIOLOGICAL REVIEWS   Vol. 79 No. 1 January 1999, pp. S145-S166
Copyright ©1999 The American Physiological Society

CFTR Is a Conductance Regulator as well as a Chloride Channel

ERIK M. SCHWIEBERT, DALE J. BENOS, MARIE E. EGAN, M. JACKSON STUTTS, AND WILLIAM B. GUGGINO

Department of Physiology and Biophysics, Gregory Fleming James CF Research Center, University of Alabama at Birmingham, Birmingham, Alabama; Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut; Department of Medicine, UNC CF Research Group, University of North Carolina, Chapel Hill, North Carolina; and Department of Physiology and Division of Pediatrics, Department of Medicine, Johns Hopkins CF Research Group, Johns Hopkins University School of Medicine, Baltimore, Maryland

Schwiebert, Erik M., Dale J. Benos, Marie E. Egan, M. Jackson Stutts, and William B. Guggino. CFTR Is a Conductance Regulator as well as a Chloride Channel. Physiol. Rev. 79, Suppl.: S145-S166, 1999.  Cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette (ABC) transporter gene family. Although CFTR has the structure of a transporter that transports substrates across the membrane in a nonconductive manner, CFTR also has the intrinsic ability to conduct Cl at much higher rates, a function unique to CFTR among this family of ABC transporters. Because Cl transport was shown to be lost in cystic fibrosis (CF) epithelia long before the cloning of the CF gene and CFTR, CFTR Cl channel function was considered to be paramount. Another equally valid perspective of CFTR, however, derives from its membership in a family of transporters that transports a multitude of different substances from chemotherapeutic drugs, to amino acids, to glutathione conjugates, to small peptides in a nonconductive manner. Moreover, at least two members of this ABC transporter family (mdr-1, SUR) can regulate other ion channels in the membrane. More simply, ABC transporters can regulate somehow the function of other cellular proteins or cellular functions. This review focuses on a plethora of studies showing that CFTR also regulates other ion channel proteins. It is the hope of the authors that the reader will take with him or her the message that CFTR is a conductance regulator as well as a Cl channel.

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