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Science 22 February 1991:
Vol. 251. no. 4996, pp. 939 - 942
DOI: 10.1126/science.2000494
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Articles

Science, Vol 251, Issue 4996, 939-942
Copyright © 1991 by American Association for the Advancement of Science

articles

Mutations affecting internal TEA blockade identify the probable pore-forming region of a K+ channel

G Yellen, ME Jurman, T Abramson, and R MacKinnon

Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

The active site of voltage-activated potassium channels is a transmembrane aqueous pore that permits ions to permeate the cell membrane in a rapid yet highly selective manner. A useful probe for the pore of potassium-selective channels is the organic ion tetraethylammonium (TEA), which binds with millimolar affinity to the intracellular opening of the pore and blocks potassium current. In the potassium channel encoded by the Drosophila Shaker gene, an amino acid residue that specifically affects the affinity for intracellular TEA has now been identified by site-directed mutagenesis. This residue is in the middle of a conserved stretch of 18 amino acids that separates two locations that are both near the external opening of the pore. These findings suggest that this conserved region is intimately involved in the formation of the ion conduction pore of voltage-activated potassium channels. Further, a stretch of only eight amino acid residues must traverse 80 percent of the transmembrane electric potential difference.


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Alternative Splicing in the Pore-Forming Region of shaker Potassium Channels.
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Scanning mutagenesis of the putative transmembrane segments of Kir2.1, an inward rectifier potassium channel.
A. Collins, H.-h. Chuang, Y. N. Jan, and L. Y. Jan (1997)
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Two functionally distinct subsites for the binding of internal blockers to the pore of voltage-activated K+ channels.
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R. A. Schwalbe, Z. Wang, L. Bianchi, and A. M. Brown (1996)
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Class III Antiarrhythmic Effects of Zatebradine: Time-, State-, Use-, and Voltage-Dependent Block of hKv1.5 Channels.
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Molecular Analysis of a Binding Site for Quinidine in a Human Cardiac Delayed Rectifier K+ Channel : Role of S6 in Antiarrhythmic Drug Binding.
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Circ. Res. 78, 1105-1114
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Inward Rectification and Implications for Cardiac Excitability.
C.G. Nichols, E.N. Makhina, W.L. Pearson, Q. Sha, and A.N. Lopatin (1996)
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Determinants of Antiarrhythmic Drug Action : Electrostatic and Hydrophobic Components of Block of the Human Cardiac hKv1.5 Channel.
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Circ. Res. 77, 575-583
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Alcohols Inhibit a Cloned Potassium Channel at a Discrete Saturable Site.
M. Covarrubias, T. B. Vyas, L. Escobar, and A. Wei (1995)
J. Biol. Chem. 270, 19408-19416
   Abstract »    Full Text »    PDF »
Silver as a probe of pore-forming residues in a potassium channel.
Q Lu and C Miller (1995)
Science 268, 304-307
   Abstract »    PDF »
Revealing the architecture of a K+ channel pore through mutant cycles with a peptide inhibitor.
P Hidalgo and R MacKinnon (1995)
Science 268, 307-310
   Abstract »    PDF »
A Topological Analysis of Goldfish Kainate Receptors Predicts Three Transmembrane Segments.
Z. G. Wo and R. E. Oswald (1995)
J. Biol. Chem. 270, 2000-2009
   Abstract »    Full Text »    PDF »
Folding pattern diversity of integral membrane proteins.
S. Cowan and J. Rosenbusch (1994)
Science 264, 914-916
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Specification of pore properties by the carboxyl terminus of inwardly rectifying K+ channels.
M Taglialatela, B. Wible, R Caporaso, and A. Brown (1994)
Science 264, 844-847
   Abstract »    PDF »
Functional stoichiometry of Shaker potassium channel inactivation.
R MacKinnon, R. Aldrich, and A. Lee (1993)
Science 262, 757-759
   Abstract »    PDF »
A mechanism for ion selectivity in potassium channels: computational studies of cation-pi interactions.
R. Kumpf and D. Dougherty (1993)
Science 261, 1708-1710
   Abstract »    PDF »
Expression of an inward-rectifying potassium channel by the Arabidopsis KAT1 cDNA.
D. Schachtman, J. Schroeder, W. Lucas, J. Anderson, and R. Gaber (1992)
Science 258, 1654-1658
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A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels.
L Heginbotham, T Abramson, and R MacKinnon (1992)
Science 258, 1152-1155
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Acetylcholine receptor channel structure probed in cysteine-substitution mutants.
M. Akabas, D. Stauffer, M Xu, and A Karlin (1992)
Science 258, 307-310
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Specification of subunit assembly by the hydrophilic amino-terminal domain of the Shaker potassium channel.
M Li, Y. Jan, and L. Jan (1992)
Science 257, 1225-1230
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Molecular localization of an ion-binding site within the pore of mammalian sodium channels.
P. Backx, D. Yue, J. Lawrence, E Marban, and G. Tomaselli (1992)
Science 257, 248-251
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Cloning and expression in yeast of a plant potassium ion transport system.
H Sentenac, N Bonneaud, M Minet, F Lacroute, J. Salmon, F Gaymard, and C Grignon (1992)
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Molecular basis of gating charge immobilization in Shaker potassium channels.
F Bezanilla, E Perozo, D. Papazian, and E Stefani (1991)
Science 254, 679-683
   Abstract »    PDF »
Similarities in amino acid sequences of Drosophila eag and cyclic nucleotide-gated channels.
H. Guy, Durell SR, J Warmke, R Drysdale, and B Ganetzky (1991)
Science 254, 730
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A component of calcium-activated potassium channels encoded by the Drosophila slo locus.
N. Atkinson, G. Robertson, and B Ganetzky (1991)
Science 253, 551-555
   Abstract »    PDF »
A distinct potassium channel polypeptide encoded by the Drosophila eag locus.
J Warmke, R Drysdale, and B Ganetzky (1991)
Science 252, 1560-1562
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Exchange of conduction pathways between two related K+ channels.
H. Hartmann, G. Kirsch, J. Drewe, M Taglialatela, R. Joho, and A. Brown (1991)
Science 251, 942-944
   Abstract »    PDF »


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