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Mechanism of Iodide/Chloride Exchange by Pendrin

Division of Regenerative Medicine and Therapeutics (A.Y., I.H., N.S., Y.Y., J.M., O.I., C.S.), Department of Genetics and Regenerative Medicine, Tottori University Graduate School of Medicine, and First Department of Internal Medicine (A.Y., S.T., Y.Y., J.M., H.F., H.S., T.Oka., T.Oku., O.I., C.S.), Tottori University Faculty of Medicine, Yonago, Tottori 683-8504, Japan; Genome Technology Branch (E.D.G.), National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892; Ohio University School of Osteopathic Medicine and Edison Biotechnology Institute (L.D.K.), Athens, Ohio 45701; and Department of Microbiology (K.S.), Leprosy Research Center, National Institute of Infectious Diseases, Tokyo 189-0002, Japan

Address all correspondence and requests for reprints to: Dr. Akio Yoshida, First Department of Internal Medicine, Tottori University Faculty of Medicine, 36-1 Nishimachi, Yonago, Tottori 683-8504, Japan. E-mail: ayoshida{at}bronze.ocn.ne.jp.

We performed an electrophysiological study to investigate ion transport of pendrin and thereby understand the pathogenesis of Pendred syndrome. Using pendrin-transfected COS-7 cells, we could show that pendrin transports both iodide and chloride measured as voltage-dependent inward and outward membrane currents. Chloride in the culture medium, [Cl^–]_o, was efficiently exchanged with cytoplasmic iodide, [I^–]_i, under physiological concentrations, indicating that pendrin is important for chloride uptake and iodide efflux. Although exchange of iodide in the medium, [I^–]_o, with cytoplasmic chloride, [Cl^–]_i, was observed, a significantly high concentration of iodide (10 mM) was required. In addition, either iodide or chloride was required on both sides of the cell membrane for the anion exchange activity of pendrin, indicating that iodide and chloride activate the exchange activity of pendrin while they are transported. The present study further supports that pendrin is responsible for the iodide efflux in thyroid cells where intracellular iodide concentration is high and that the general function of pendrin in other tissues is to transport chloride through exchange with other anions.