Mechanism of iodide/chloride exchange by pendrin.
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.
Yoshida
Akio
A
Division of Regenerative Medicine and Therapeutics, Tottori University Faculty of Medicine, 36-1 Nishimachi, Yonago, Tottori 683-8504, Japan. ayoshida@bronze.ocn.ne.jp.
Hisatome
Ichiro
I
Taniguchi
Shinichi
S
Sasaki
Norihiro
N
Yamamoto
Yasutaka
Y
Miake
Junichiro
J
Fukui
Hiroko
H
Shimizu
Hideki
H
Okamura
Tomohisa
T
Okura
Tsuyoshi
T
Igawa
Osamu
O
Shigemasa
Chiaki
C
Green
Eric D
ED
Kohn
Leonard D
LD
Suzuki
Koichi
K
D000818:Animals; D000838:Anions / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002712:Chlorides / Q000493:pharmacokinetics*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007454:Iodides / Q000493:pharmacokinetics*; D008564:Membrane Potentials / Q000502:physiology; D026901:Membrane Transport Proteins; D018408:Patch-Clamp Techniques; D000076988:Sulfate Transporters; D014162:Transfection
D000838:Anions; D002352:Carrier Proteins; D002712:Chlorides; D007454:Iodides; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters