Abstract
ION channels selectively permeable to chloride ions regulate cell functions as diverse as excitability and control of cell volume1–5. Using expression cloning techniques, a complementary DNA from an epithelial cell line has been isolated, sequenced and its putative structure examined by site-directed mutagenesis. This cDNA, encoding a 235-amino-acid protein, gave rise to a chloride-selective outward current when expressed in Xenopus oocytes. The expressed, outwardly rectifying chloride current was calcium-insensitive and was blocked by nucleotides applied to the cell surface. Mutation of a putative nucleotide-binding site resulted in loss of nucleotide block but incurred dependence on extracellular calcium concentration. The unusual sequence of this putative channel protein suggests a new class of ion channels not related to other previously cloned chloride channels6–11.
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References
Lang, F., Völkl, H. & Häussinger, D. Comp. Physiol. 4, 1–25 (1990).
Hoffmann, E. K. & Simonsen, L. O. Physiol. Rev. 69, 315–382 (1989).
Worrell, R. T., Butt, A. G., Cliff, W. H. & Frizzell, R. A. Am. J. Physiol. 256, 1111–1119 (1989).
Solc, C. K. & Wine, J. J. Am. J. Physiol. 261, 658–674 (1991).
Bretag, A. H. Physiol. Rev. 67, 618–724 (1987).
Rich, D. P. et al. Nature 347, 358–363 (1990).
Drumm, M. L. et al. Cell 62, 1227–1233 (1990).
Frizzell, R. A. Trends Neurosci. 10, 190–193 (1987).
Quinton, P. M. FASEB J. 4, 2709–2717 (1990).
Anderson, M. P. et al. Science 253, 202–205 (1991).
Jentsch, T. J., Steinmeyer, K. & Schwartz, G. Nature 348, 510–514 (1990).
Kolb, H. A., Brown, C. & Murer, H. Pflügers Arch. 403, 262–265 (1985).
Paulmichl, M., Wöll, E. & Lang, F. FEBS Lett. 234, 263–266 (1988).
Lang, F., Defregger, M. & Paulmichl, M. Pflügers Arch. 407, 158–162 (1986).
Paulmichl, M., Friedrich, F., Maly, K. & Lang, F. Pflügers Arch. 413, 456–462 (1989).
Hille, B. Ionic channels of Excitable Membranes (Sinauer, Sunderland, MA, 1984).
Dascal, N. CRC Crit. Rev. Biochem. 22, 317–387 (1987).
Wangemann, P. et al. Pflügers Arch. 407, S141 (1986).
Guy, H. R. Biophys. J. 47, 61–70 (1985).
Blachly-Dyson, E., Peng, S., Colombini, M. & Forte, M. Science 247, 1233–1236 (1990).
Saraste, M., Sibbald, P. R. & Wittinghofer, A. Trends biochem. Sci. 15, 430–434 (1990).
Cliff, W. H. & Frizell, R. A. Proc. natn. Acad. Sci. U.S.A. 87, 4956–4960 (1990).
Anderson, M. P. & Welsh, M. J. Proc. natn. Acad. Sci. U.S.A. 88, 6003–6007 (1991).
Lechleiter, J. et al. EMBO J. 9, 4381–4390 (1990).
Lechleiter, J., Girard, S., Clapham, D. & Peralta, E. Nature 350, 505–508 (1991).
Lechleiter, J., Girard, S., Peralta, E. & Clapham, D. Science, 252, 123–126 (1991).
Maniatis, T., Fritsch, E. & Sambrook, J. Molecular Cloning, A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1982).
Tabor, S. & Richardson, C. Proc. natn. Acad. Sci. U.S.A. 84, 4767–4771 (1987).
Heizmann, C. W. & Hunziker, W. Trends biochem. Sci. 16, 98–103 (1991).
Kunkel, T. A. Proc. natn. Acad. Sci. U.S.A. 82, 488–492 (1985).
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Paulmichl, M., Li, Y., Wickman, K. et al. New mammalian chloride channel identified by expression cloning. Nature 356, 238–241 (1992). https://doi.org/10.1038/356238a0
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DOI: https://doi.org/10.1038/356238a0
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