Home LiteratureArticle Details
PMID: 19092925 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Review

Sensing voltage across lipid membranes.

Nature ·Vol. 456 ·No. 7224 ·2008-12-18 ·Pages 891-7

Swartz KJ

Abstract

The detection of electrical potentials across lipid bilayers by specialized membrane proteins is required for many fundamental cellular processes such as the generation and propagation of nerve impulses. These membrane proteins possess modular voltage-sensing domains, a notable example being the S1-S4 domains of voltage-activated ion channels. Ground-breaking structural studies on these domains explain how voltage sensors are designed and reveal important interactions with the surrounding lipid membrane. Although further structures are needed to understand the conformational changes that occur during voltage sensing, the available data help to frame several key concepts that are fundamental to the mechanism of voltage sensing.

MeSH Terms
Animals Cell Membrane/metabolism Humans Ion Channel Gating Membrane Lipids/metabolism Membrane Proteins/chemistry,metabolism Movement Protein Structure, Tertiary
Chemicals
Membrane Lipids Membrane Proteins
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Swartz Kenton J
Porter Neuroscience Research Center, Molecular Physiology and Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. swartzk@ninds.nih.gov
References (86)
86 references, click to expand
  1. Molecular properties of voltage-sensitive sodium channels.
    Annu Rev Biochem. 1986;55:953-85 PMID: 2427018
  2. Structure of the transmembrane regions of a bacterial cyclic nucleotide-regulated channel.
    Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1511-5 PMID: 18216238
  3. Inferred motions of the S3a helix during voltage-dependent K+ channel gating.
    J Mol Biol. 2008 Sep 5;381(3):569-80 PMID: 18632115
  4. Molecular model of the action potential sodium channel.
    Proc Natl Acad Sci U S A. 1986 Jan;83(2):508-12 PMID: 2417247
  5. Portability of paddle motif function and pharmacology in voltage sensors.
    Nature. 2007 Nov 15;450(7168):370-5 PMID: 18004375
  6. A voltage-gated proton-selective channel lacking the pore domain.
    Nature. 2006 Apr 27;440(7088):1213-6 PMID: 16554753
  7. Molecular basis of charge movement in voltage-gated sodium channels.
    Neuron. 1996 Jan;16(1):113-22 PMID: 8562074
  8. A fluorometric approach to local electric field measurements in a voltage-gated ion channel.
    Neuron. 2003 Jan 9;37(1):85-97 PMID: 12526775
  9. The size of gating charge in wild-type and mutant Shaker potassium channels.
    Science. 1992 Mar 27;255(5052):1712-5 PMID: 1553560
  10. Transmembrane movement of the shaker K+ channel S4.
    Neuron. 1996 Feb;16(2):387-97 PMID: 8789953
  11. Primary structure of the receptor for calcium channel blockers from skeletal muscle.
    Nature. 1987 Jul 23-29;328(6128):313-8 PMID: 3037387
  12. Structural implications of fluorescence quenching in the Shaker K+ channel.
    J Gen Physiol. 1998 Oct;112(4):391-408 PMID: 9758859
  13. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
    Science. 2005 Aug 5;309(5736):897-903 PMID: 16002581
  14. Interface connections of a transmembrane voltage sensor.
    Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15059-64 PMID: 16217012
  15. How does a voltage sensor interact with a lipid bilayer? Simulations of a potassium channel domain.
    Structure. 2007 Feb;15(2):235-44 PMID: 17292841
  16. Localization and molecular determinants of the Hanatoxin receptors on the voltage-sensing domains of a K(+) channel.
    J Gen Physiol. 2000 Jun;115(6):673-84 PMID: 10828242
  17. Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer.
    Science. 2004 Oct 15;306(5695):491-5 PMID: 15486302
  18. Contribution of the S4 segment to gating charge in the Shaker K+ channel.
    Neuron. 1996 Jun;16(6):1169-77 PMID: 8663993
  19. Spectroscopic mapping of voltage sensor movement in the Shaker potassium channel.
    Nature. 1999 Dec 16;402(6763):813-7 PMID: 10617202
  20. Extent of voltage sensor movement during gating of shaker K+ channels.
    Neuron. 2008 Jul 10;59(1):98-109 PMID: 18614032
  21. Small vertical movement of a K+ channel voltage sensor measured with luminescence energy transfer.
    Nature. 2005 Aug 11;436(7052):848-51 PMID: 16094368
  22. Closing in on the resting state of the Shaker K(+) channel.
    Neuron. 2007 Oct 4;56(1):124-40 PMID: 17920020
  23. Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.
    Neuron. 1996 Jun;16(6):1159-67 PMID: 8663992
  24. Dimeric subunit stoichiometry of the human voltage-dependent proton channel Hv1.
    Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7692-5 PMID: 18509058
  25. Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
    Science. 2005 Aug 5;309(5736):903-8 PMID: 16002579
  26. Structural dynamics of an isolated voltage-sensor domain in a lipid bilayer.
    Structure. 2008 Mar;16(3):398-409 PMID: 18334215
  27. Kinetics and steady-state properties of the charged system controlling sodium conductance in the squid giant axon.
    J Physiol. 1974 Jun;239(2):393-434 PMID: 4414038
  28. Mutations in the S4 region isolate the final voltage-dependent cooperative step in potassium channel activation.
    J Gen Physiol. 1999 Mar;113(3):389-414 PMID: 10051516
  29. The principle of gating charge movement in a voltage-dependent K+ channel.
    Nature. 2003 May 1;423(6935):42-8 PMID: 12721619
  30. Tarantula toxins interact with voltage sensors within lipid membranes.
    J Gen Physiol. 2007 Nov;130(5):497-511 PMID: 17938232
  31. Direct physical measure of conformational rearrangement underlying potassium channel gating.
    Science. 1996 Jan 12;271(5246):213-6 PMID: 8539623
  32. Functional analysis of an archaebacterial voltage-dependent K+ channel.
    Nature. 2003 Mar 13;422(6928):180-5 PMID: 12629550
  33. Evidence for voltage-dependent S4 movement in sodium channels.
    Neuron. 1995 Jul;15(1):213-8 PMID: 7619524
  34. The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor.
    Neuron. 2008 May 22;58(4):546-56 PMID: 18498736
  35. Measurement of the movement of the S4 segment during the activation of a voltage-gated potassium channel.
    Pflugers Arch. 1996 Nov-Dec;433(1-2):91-7 PMID: 9019737
  36. Voltage-sensor activation with a tarantula toxin as cargo.
    Nature. 2005 Aug 11;436(7052):857-60 PMID: 16094370
  37. A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom.
    Nature. 2004 Jul 8;430(6996):232-5 PMID: 15241419
  38. Two atomic constraints unambiguously position the S4 segment relative to S1 and S2 segments in the closed state of Shaker K channel.
    Proc Natl Acad Sci U S A. 2007 May 8;104(19):7904-9 PMID: 17470814
  39. Electrostatic interactions of S4 voltage sensor in Shaker K+ channel.
    Neuron. 1995 Jun;14(6):1293-301 PMID: 7605638
  40. Voltage-sensing arginines in a potassium channel permeate and occlude cation-selective pores.
    Neuron. 2005 Feb 3;45(3):379-88 PMID: 15694325
  41. Calibrated measurement of gating-charge arginine displacement in the KvAP voltage-dependent K+ channel.
    Cell. 2005 Nov 4;123(3):463-75 PMID: 16269337
  42. Coupling between voltage sensors and activation gate in voltage-gated K+ channels.
    J Gen Physiol. 2002 Nov;120(5):663-76 PMID: 12407078
  43. Electrostatics and the gating pore of Shaker potassium channels.
    J Gen Physiol. 2001 Jan;117(1):69-89 PMID: 11134232
  44. Focused electric field across the voltage sensor of potassium channels.
    Neuron. 2005 Oct 6;48(1):25-9 PMID: 16202706
  45. alpha-helical structural elements within the voltage-sensing domains of a K(+) channel.
    J Gen Physiol. 2000 Jan;115(1):33-50 PMID: 10613917
  46. Removal of phospho-head groups of membrane lipids immobilizes voltage sensors of K+ channels.
    Nature. 2008 Feb 14;451(7180):826-9 PMID: 18273018
  47. Phospholipids and the origin of cationic gating charges in voltage sensors.
    Nature. 2006 Dec 7;444(7120):775-9 PMID: 17136096
  48. The orientation and molecular movement of a k(+) channel voltage-sensing domain.
    Neuron. 2003 Oct 30;40(3):515-25 PMID: 14642276
  49. Histidine scanning mutagenesis of basic residues of the S4 segment of the shaker k+ channel.
    J Gen Physiol. 2001 May;117(5):469-90 PMID: 11331357
  50. Voltage dependent charge movement of skeletal muscle: a possible step in excitation-contraction coupling.
    Nature. 1973 Mar 23;242(5395):244-6 PMID: 4540479
  51. X-ray structure of a voltage-dependent K+ channel.
    Nature. 2003 May 1;423(6935):33-41 PMID: 12721618
  52. Dynamics of the Kv1.2 voltage-gated K+ channel in a membrane environment.
    Biophys J. 2007 Nov 1;93(9):3070-82 PMID: 17704179
  53. Reconstructing voltage sensor-pore interaction from a fluorescence scan of a voltage-gated K+ channel.
    Neuron. 2000 Sep;27(3):585-95 PMID: 11055440
  54. Expression of functional sodium channels from cloned cDNA.
    Nature. 1986 Aug 28-Sep 3;322(6082):826-8 PMID: 2427955
  55. Primary structure and functional expression of a mouse inward rectifier potassium channel.
    Nature. 1993 Mar 11;362(6416):127-33 PMID: 7680768
  56. Helical structure and packing orientation of the S2 segment in the Shaker K+ channel.
    J Gen Physiol. 1999 Mar;113(3):415-23 PMID: 10051517
  57. Atomic scale movement of the voltage-sensing region in a potassium channel measured via spectroscopy.
    Nature. 1999 Dec 16;402(6763):809-13 PMID: 10617201
  58. Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites.
    Neuron. 1997 Apr;18(4):665-73 PMID: 9136774
  59. Ion permeation through a voltage- sensitive gating pore in brain sodium channels having voltage sensor mutations.
    Neuron. 2005 Jul 21;47(2):183-9 PMID: 16039561
  60. The structure of the lipid-embedded potassium channel voltage sensor determined by double-electron-electron resonance spectroscopy.
    Protein Sci. 2008 Mar;17(3):506-17 PMID: 18287283
  61. Movement and crevices around a sodium channel S3 segment.
    J Gen Physiol. 2002 Sep;120(3):419-36 PMID: 12198095
  62. Ion conduction pore is conserved among potassium channels.
    Nature. 2001 Oct 25;413(6858):809-13 PMID: 11677598
  63. Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor.
    Nature. 2005 Jun 30;435(7046):1239-43 PMID: 15902207
  64. Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels.
    Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8585-9 PMID: 9671721
  65. The voltage-gated potassium channels and their relatives.
    Nature. 2002 Sep 5;419(6902):35-42 PMID: 12214225
  66. Helical structure of the COOH terminus of S3 and its contribution to the gating modifier toxin receptor in voltage-gated ion channels.
    J Gen Physiol. 2001 Mar;117(3):205-18 PMID: 11222625
  67. Currents related to movement of the gating particles of the sodium channels.
    Nature. 1973 Apr 13;242(5398):459-61 PMID: 4700900
  68. Enzymatic activation of voltage-gated potassium channels.
    Nature. 2006 Aug 10;442(7103):696-9 PMID: 16799569
  69. Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila.
    Science. 1987 Aug 14;237(4816):770-5 PMID: 2441471
  70. Specificity of charge-carrying residues in the voltage sensor of potassium channels.
    J Gen Physiol. 2004 Mar;123(3):205-16 PMID: 14769847
  71. Characterizing voltage-dependent conformational changes in the Shaker K+ channel with fluorescence.
    Neuron. 1997 Nov;19(5):1127-40 PMID: 9390525
  72. Voltage-dependent proton transport by the voltage sensor of the Shaker K+ channel.
    Neuron. 1997 Dec;19(6):1319-27 PMID: 9427254
  73. Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.
    Neuron. 2006 Nov 22;52(4):623-34 PMID: 17114047
  74. Atomic proximity between S4 segment and pore domain in Shaker potassium channels.
    Neuron. 2003 Jul 31;39(3):467-81 PMID: 12895421
  75. A proton pore in a potassium channel voltage sensor reveals a focused electric field.
    Nature. 2004 Feb 5;427(6974):548-53 PMID: 14765197
  76. Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
    Nature. 2007 Nov 15;450(7168):376-82 PMID: 18004376
  77. Structure prediction for the down state of a potassium channel voltage sensor.
    Nature. 2007 Feb 1;445(7127):550-3 PMID: 17187053
  78. The lipid-protein interface of a Shaker K(+) channel.
    J Gen Physiol. 2000 Jan;115(1):51-8 PMID: 10613918
  79. Gating charge displacement in voltage-gated ion channels involves limited transmembrane movement.
    Nature. 2005 Aug 11;436(7052):852-6 PMID: 16094369
  80. Effective gating charges per channel in voltage-dependent K+ and Ca2+ channels.
    J Gen Physiol. 1996 Sep;108(3):143-55 PMID: 8882860
  81. A quantitative description of membrane current and its application to conduction and excitation in nerve.
    J Physiol. 1952 Aug;117(4):500-44 PMID: 12991237
  82. A voltage-sensor water pore.
    Biophys J. 2006 Dec 1;91(11):L90-2 PMID: 17012321
  83. Constraints on voltage sensor movement in the shaker K+ channel.
    J Gen Physiol. 2006 Dec;128(6):687-99 PMID: 17101817
  84. Subunit organization and functional transitions in Ci-VSP.
    Nat Struct Mol Biol. 2008 Jan;15(1):106-8 PMID: 18084307
  85. Deconstructing voltage sensor function and pharmacology in sodium channels.
    Nature. 2008 Nov 13;456(7219):202-8 PMID: 19005548
  86. A voltage sensor-domain protein is a voltage-gated proton channel.
    Science. 2006 Apr 28;312(5773):589-92 PMID: 16556803
Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature07620
Email
swartzk@ninds.nih.gov
Published
2008-12-18
Pages
891-7
Language
English
Region
England
NLM ID
0410462
PMCID
PMC2629456
Subset
IM
Grants
Intramural NIH HHS · ZIA NS002945-13 · United States
External Links
PubMed source DOI: 10.1038/nature07620 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2