In nerve and muscle cells, the voltage-gated opening and closing of cation-selective ion channels is accompanied by the translocation of 12–14 elementary charges across the membrane's electric field. Although most of these charges are carried by residues in the S4 helix of the gating module of these channels, the precise nature of their physical movement is currently the topic of spirited debate. Broadly speaking, two classes of models have emerged: those that suggest that small-scale motions can account for the extensive charge displacement, and those that invoke a much larger physical movement. In the most recent incarnation of the latter type of model, which is based on structural and functional data from the archaebacterial K+ channel KvAP, a “voltage-sensor paddle” comprising a helix-turn-helix of S3–S4 translocates ∼20 Å through the bilayer during the gating cycle (Jiang, Y., A. Lee, J. Chen, V. Ruta, M. Cadene, B.T. Chait, and R. MacKinnon. 2003. Nature. 423:33–41; Jiang, Y., V. Ruta, J. Chen, A. Lee, and R. MacKinnon. 2003. Nature. 423:42–48.; Ruta, V., J. Chen, and R. MacKinnon. 2005. Cell. 123:463–475). We used two methods to test for analogous motions in the Shaker K+ channel, each examining the aqueous exposure of residues near S3. In the first, we employed a pore-blocking maleimide reagent (Blaustein, R.O., P.A. Cole, C. Williams, and C. Miller. 2000. Nat. Struct. Biol. 7:309–311) to probe for state-dependent changes in the chemical reactivity of substituted cysteines; in the second, we tested the state-dependent accessibility of a tethered biotin to external streptavidin (Qiu, X.Q., K.S. Jakes, A. Finkelstein, and S.L. Slatin. 1994. J. Biol. Chem. 269:7483–7488; Slatin, S.L., X.Q. Qiu, K.S. Jakes, and A. Finkelstein. 1994. Nature. 371:158–161). In both types of experiments, residues predicted to lie near the top of S3 did not exhibit any change in aqueous exposure during the gating cycle. This lack of state dependence argues against large-scale movements, either axially or radially, of Shaker's S3–S4 voltage-sensor paddle.
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1 December 2006
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November 13 2006
Constraints on Voltage Sensor Movement in the Shaker K+ Channel
Rachel B. Darman,
Rachel B. Darman
1Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA 02111
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Allison A. Ivy,
Allison A. Ivy
1Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA 02111
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Vina Ketty,
Vina Ketty
1Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA 02111
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Robert O. Blaustein
Robert O. Blaustein
1Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA 02111
2Department of Neuroscience, Tufts Medical School, Boston, MA 02111
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Rachel B. Darman
1Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA 02111
Allison A. Ivy
1Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA 02111
Vina Ketty
1Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA 02111
Robert O. Blaustein
1Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA 02111
2Department of Neuroscience, Tufts Medical School, Boston, MA 02111
Correspondence to Robert O. Blaustein: [email protected]
R.B. Darman and A.A. Ivy contributed equally to this work.
A.A. Ivy's present address is Abbott Laboratories, Abbott Park, IL 60064.
V. Ketty's present address is BD Biosciences, Bedford, MA 01730.
Abbreviations used in this paper: MTS, methanethiosulfonate; MTSET, methanethiosulfonate ethyltriethylammonium; QA, quaternary ammonium.
Received:
July 06 2006
Accepted:
October 25 2006
Online ISSN: 1540-7748
Print ISSN: 0022-1295
The Rockefeller University Press
2006
J Gen Physiol (2006) 128 (6): 687–699.
Article history
Received:
July 06 2006
Accepted:
October 25 2006
Citation
Rachel B. Darman, Allison A. Ivy, Vina Ketty, Robert O. Blaustein; Constraints on Voltage Sensor Movement in the Shaker K+ Channel . J Gen Physiol 1 December 2006; 128 (6): 687–699. doi: https://doi.org/10.1085/jgp.200609624
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