shaker superfamily of potassium channels


Summary: Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.

Top Publications

  1. Cuello L, Jogini V, Cortes D, Pan A, Gagnon D, Dalmas O, et al. Structural basis for the coupling between activation and inactivation gates in K(+) channels. Nature. 2010;466:272-5 pubmed publisher
    ..We propose that side-chain rearrangements at position 103 mechanically couple activation and inactivation in KcsA and a variety of other K(+) channels...
  2. del Camino D, Yellen G. Tight steric closure at the intracellular activation gate of a voltage-gated K(+) channel. Neuron. 2001;32:649-56 pubmed
    ..Either these Kv channels have a broader inner entrance than seen in the KcsA crystal, even in the closed state, or the region is highly flexible (but nevertheless remains very securely closed nearby). ..
  3. Duzhyy D, Sakai Y, Sokolowski B. Cloning and developmental expression of Shaker potassium channels in the cochlea of the chicken. Brain Res Mol Brain Res. 2004;121:70-85 pubmed
    ..This expression pattern suggests the potential for the formation of heteromeric channels from the corresponding alpha-subunits in these various tissues. ..
  4. Lacroix J, Labro A, Bezanilla F. Properties of deactivation gating currents in Shaker channels. Biophys J. 2011;100:L28-30 pubmed publisher
    ..We propose a new (to our knowledge) kinetic model that accounts for these observations. ..
  5. Jogini V, Roux B. Electrostatics of the intracellular vestibule of K+ channels. J Mol Biol. 2005;354:272-88 pubmed
  6. Soler Llavina G, Holmgren M, Swartz K. Defining the conductance of the closed state in a voltage-gated K+ channel. Neuron. 2003;38:61-7 pubmed
    ..16 fS, or at least 100,000 times lower than for the open state of the channel, indicating that the flow of ions is very tightly regulated in this class of K+ channels. ..
  7. Lecar H, Larsson H, Grabe M. Electrostatic model of S4 motion in voltage-gated ion channels. Biophys J. 2003;85:2854-64 pubmed
    ..The resulting gating-charge distributions are compared to experimental results on wild-type and charge-neutralized mutants of the Shaker K(+) channel. ..
  8. Ahern C, Horn R. Specificity of charge-carrying residues in the voltage sensor of potassium channels. J Gen Physiol. 2004;123:205-16 pubmed
    ..This remarkable specificity indicates that charge movement involves highly specialized interactions between the voltage sensor and other regions of the protein, a mechanism inconsistent with the paddle model. ..
  9. Elliott D, Neale E, Aziz Q, Dunham J, Munsey T, Hunter M, et al. Molecular mechanism of voltage sensor movements in a potassium channel. EMBO J. 2004;23:4717-26 pubmed

More Information


  1. Panyi G, Deutsch C. Cross talk between activation and slow inactivation gates of Shaker potassium channels. J Gen Physiol. 2006;128:547-59 pubmed
    ..Because activation and slow inactivation are ubiquitous gating processes in potassium channels, the cross talk between them is likely to be a fundamental factor in controlling ion flux across membranes. ..
  2. Koh K, Joiner W, Wu M, Yue Z, Smith C, Sehgal A. Identification of SLEEPLESS, a sleep-promoting factor. Science. 2008;321:372-6 pubmed publisher
    ..Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability. ..
  3. Naranjo D, Miller C. A strongly interacting pair of residues on the contact surface of charybdotoxin and a Shaker K+ channel. Neuron. 1996;16:123-30 pubmed
    ..The known position of CTX-29 on the toxin's interaction surface thus locates Shaker-449 within 5 A of the pore axis of the closed channel. All four subunits must carry the 449F mutation to produce a highly toxin-insensitive channel. ..
  4. Starace D, Stefani E, Bezanilla F. Voltage-dependent proton transport by the voltage sensor of the Shaker K+ channel. Neuron. 1997;19:1319-27 pubmed
    ..The remarkable implication of the successive exposure of histidine to each side of the membrane is that in a pH gradient, the voltage sensor transports protons. ..
  5. Lu Z, Klem A, Ramu Y. Coupling between voltage sensors and activation gate in voltage-gated K+ channels. J Gen Physiol. 2002;120:663-76 pubmed
    ..One sequence is the so called S4-S5 linker distal to the voltage-sensing S4, while the other is around the COOH-terminal end of S6, a region containing the actual gate-forming residues. ..
  6. Soler Llavina G, Chang T, Swartz K. Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel. Neuron. 2006;52:623-34 pubmed
  7. Gagnon D, Bezanilla F. The contribution of individual subunits to the coupling of the voltage sensor to pore opening in Shaker K channels: effect of ILT mutations in heterotetramers. J Gen Physiol. 2010;136:555-68 pubmed publisher
  8. Lee J, Ueda A, Wu C. Pre- and post-synaptic mechanisms of synaptic strength homeostasis revealed by slowpoke and shaker K+ channel mutations in Drosophila. Neuroscience. 2008;154:1283-96 pubmed publisher
  9. Lin M, Hsieh J, Mock A, Papazian D. R1 in the Shaker S4 occupies the gating charge transfer center in the resting state. J Gen Physiol. 2011;138:155-63 pubmed publisher
    ..Our results strongly support the conclusion that R1 occupies the gating charge transfer center in the resting conformation...
  10. Kitaguchi T, Sukhareva M, Swartz K. Stabilizing the closed S6 gate in the Shaker Kv channel through modification of a hydrophobic seal. J Gen Physiol. 2004;124:319-32 pubmed
    ..This mechanism is discussed in the context of the structure of this critical region in K+ channels. ..
  11. Poliak S, Salomon D, Elhanany H, Sabanay H, Kiernan B, Pevny L, et al. Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1. J Cell Biol. 2003;162:1149-60 pubmed
  12. Borys P, Grzywna Z. A diffusive model of the ball and chain inactivation. Biosystems. 2008;94:267-9 pubmed publisher
    ..The ball and chain mechanism is a widely accepted theory for the inactivation of the Shaker K(+)channel. In this paper we propose a diffusive model that predicts a rate of inactivation that is comparable to the experimental measurements. ..
  13. Melishchuk A, Armstrong C. Mechanism underlying slow kinetics of the OFF gating current in Shaker potassium channel. Biophys J. 2001;80:2167-75 pubmed
    ..Our results suggest that the cavity in Shaker is so small that even permeant cations like Rb+ or Cs+ must leave the cavity before the channel gate can close. ..
  14. Gomez Lagunas F. Barium inhibition of the collapse of the Shaker K(+) conductance in zero K(+). Biophys J. 1999;77:2988-98 pubmed
    ..Ba(2+) is an effective K(+) substitute, inhibiting the passage of the channels into the stable nonconducting (noninactivated) mode of gating. ..
  15. Tejedor F, Bokhari A, Rogero O, Gorczyca M, Zhang J, Kim E, et al. Essential role for dlg in synaptic clustering of Shaker K+ channels in vivo. J Neurosci. 1997;17:152-9 pubmed
    ..These studies demonstrate for the first time that DLG plays an important role in synaptic organization in vivo that correlates with its ability to bind directly to specific membrane proteins of the synapse. ..
  16. Ma Z, Wong K, Horrigan F. An extracellular Cu2+ binding site in the voltage sensor of BK and Shaker potassium channels. J Gen Physiol. 2008;131:483-502 pubmed publisher
    ..Our results suggest that the voltage sensor forms a state- and pH-dependent, metal-selective binding pocket that may be occupied by Cu2+ at physiologically relevant concentrations to inhibit activation of BK and other channels. ..
  17. Browne D, Gancher S, Nutt J, Brunt E, Smith E, Kramer P, et al. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet. 1994;8:136-40 pubmed
    ..Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/myokymia can result from mutations in this gene. ..
  18. Mosca T, Carrillo R, White B, Keshishian H. Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K+ channel subunit. Proc Natl Acad Sci U S A. 2005;102:3477-82 pubmed
    ..This finding indicates that elevated postsynaptic membrane excitability is by itself insufficient to enhance presynaptic arbor growth. Such changes must minimally involve increased neuronal excitability. ..
  19. Gonzalez C, Morera F, Rosenmann E, Alvarez O, Latorre R. S3b amino acid residues do not shuttle across the bilayer in voltage-dependent Shaker K+ channels. Proc Natl Acad Sci U S A. 2005;102:5020-5 pubmed
    ..We conclude that the S3b segment is always exposed to the external milieu of the Shaker K+ channel. Our results are incompatible with any model involving a large membrane displacement of segment S3b. ..
  20. Mannikko R, Elinder F, Larsson H. Voltage-sensing mechanism is conserved among ion channels gated by opposite voltages. Nature. 2002;419:837-41 pubmed
  21. Blaustein R. Kinetics of tethering quaternary ammonium compounds to K(+) channels. J Gen Physiol. 2002;120:203-16 pubmed
    ..This behavior is shown to arise from the ability of a strong blocker to concentrate its maleimide end near a channel's cysteine target by exploiting the reversible pore-blocking affinity of its QA headgroup. ..
  22. Lu Z, Klem A, Ramu Y. Ion conduction pore is conserved among potassium channels. Nature. 2001;413:809-13 pubmed
    ..The resulting chimaeras retain the respective functional hallmarks of the eukaryotic channels, which indicates that the ion conduction pore is indeed conserved among K+ channels. ..
  23. Mannuzzu L, Isacoff E. Independence and cooperativity in rearrangements of a potassium channel voltage sensor revealed by single subunit fluorescence. J Gen Physiol. 2000;115:257-68 pubmed
    ..Such cooperativity in gating of voltage-dependent channels has great physiological relevance since it can affect both action potential threshold and rate of propagation. ..
  24. MacKinnon R, Cohen S, Kuo A, Lee A, Chait B. Structural conservation in prokaryotic and eukaryotic potassium channels. Science. 1998;280:106-9 pubmed
    ..The results show that a prokaryotic K+ channel has the same pore structure as eukaryotic K+ channels. This structural conservation, through application of techniques presented here, offers a new approach for K+ channel pharmacology. ..
  25. Posson D, Selvin P. Extent of voltage sensor movement during gating of shaker K+ channels. Neuron. 2008;59:98-109 pubmed publisher
    ..Rather, our measurements demonstrate a moderate S4 displacement of 10 +/- 5 A, with a vertical component of 5 +/- 2 A. The S3 segment moves 2 +/- 1 A in the opposite direction and is therefore not moving as an S3-S4 rigid body. ..
  26. Bushey D, Huber R, Tononi G, Cirelli C. Drosophila Hyperkinetic mutants have reduced sleep and impaired memory. J Neurosci. 2007;27:5384-93 pubmed
    ..These data identify a gene, Hk, which is necessary to maintain normal sleep, and provide genetic evidence that short sleep and poor memory are linked. ..
  27. Baukrowitz T, Yellen G. Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel. Science. 1996;271:653-6 pubmed
    ..This slow rate probably reflected the departure of the last ion from the multi-ion pore: Permeation of ions (at 10(7) per second) occurs rapidly because of ion-ion repulsion, but the last ion to leave would experience no such repulsion. ..
  28. Street V, Tempel B. Physical mapping of potassium channel gene clusters on mouse chromosomes three and six. Genomics. 1997;44:110-7 pubmed
    ..These detailed physical maps of both K channel gene clusters provide additional support for the idea of an ancient genome tetraploidization event. ..
  29. Tan K, Lennon V, Klein C, Boeve B, Pittock S. Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology. 2008;70:1883-90 pubmed publisher
    ..Evaluation for VGKC antibodies is recommended in the comprehensive autoimmune serologic testing of subacute idiopathic neurologic disorders. ..
  30. Kleopa K, Elman L, Lang B, Vincent A, Scherer S. Neuromyotonia and limbic encephalitis sera target mature Shaker-type K+ channels: subunit specificity correlates with clinical manifestations. Brain. 2006;129:1570-84 pubmed
    ..Although more than one type of antibody is often detectable in individual sera, higher affinity for certain subunits or subunit combinations may determine the range of clinical manifestations...
  31. Bayrhuber M, Graf R, Ferber M, Zweckstetter M, Imperial J, Garrett J, et al. Production of recombinant Conkunitzin-S1 in Escherichia coli. Protein Expr Purif. 2006;47:640-4 pubmed
    ..Refolding in the presence of glutathione followed by pH shift-induced cleavage of the fusion protein resulted in a functional toxin as demonstrated by voltage-clamp measurements. ..
  32. Cha A, Bezanilla F. Characterizing voltage-dependent conformational changes in the Shaker K+ channel with fluorescence. Neuron. 1997;19:1127-40 pubmed
    ..Spectroscopy indicated that the mechanism of fluorescence change involves voltage-dependent quenching of the probe in an aqueous environment by other parts of the protein. ..
  33. Ding S, Ingleby L, Ahern C, Horn R. Investigating the putative glycine hinge in Shaker potassium channel. J Gen Physiol. 2005;126:213-26 pubmed
    ..Our results support roles for Gly466 both in biogenesis of the channel and as a hinge in activation gating. ..
  34. Cirelli C, Bushey D, Hill S, Huber R, Kreber R, Ganetzky B, et al. Reduced sleep in Drosophila Shaker mutants. Nature. 2005;434:1087-92 pubmed
    ..Shaker, which encodes a voltage-dependent potassium channel controlling membrane repolarization and transmitter release, may thus regulate sleep need or efficiency. ..
  35. Thompson J, Begenisich T. Interaction between quaternary ammonium ions in the pore of potassium channels. Evidence against an electrostatic repulsion mechanism. J Gen Physiol. 2000;115:769-82 pubmed
    ..We found that these results can be simulated by a simple 4-barrier-3-site permeation model in which ions compete for available binding sites without long-range electrostatic interactions...
  36. Sack J, Aldrich R, Gilly W. A gastropod toxin selectively slows early transitions in the Shaker K channel's activation pathway. J Gen Physiol. 2004;123:685-96 pubmed
    ..A model of BrMT action is developed that suggests BrMT rapidly binds to and stabilizes resting channel conformations. ..
  37. Asamoah O, Wuskell J, Loew L, Bezanilla F. A fluorometric approach to local electric field measurements in a voltage-gated ion channel. Neuron. 2003;37:85-97 pubmed
    ..The extension of this method to other membrane bound proteins, including transporters, will yield insight into the role of electrical forces on protein function. ..
  38. Lacroix J, Bezanilla F. Control of a final gating charge transition by a hydrophobic residue in the S2 segment of a K+ channel voltage sensor. Proc Natl Acad Sci U S A. 2011;108:6444-9 pubmed publisher
    ..Our results suggest that F(290) controls the transfer of R(371), the fourth gating charge, during gating while not affecting the movement of the other three gating arginines. ..
  39. Goldberg E, Clark B, Zagha E, Nahmani M, Erisir A, Rudy B. K+ channels at the axon initial segment dampen near-threshold excitability of neocortical fast-spiking GABAergic interneurons. Neuron. 2008;58:387-400 pubmed publisher
  40. Henrion U, Renhorn J, Börjesson S, Nelson E, Schwaiger C, Bjelkmar P, et al. Tracking a complete voltage-sensor cycle with metal-ion bridges. Proc Natl Acad Sci U S A. 2012;109:8552-7 pubmed publisher
  41. Peng I, Wu C. Differential contributions of Shaker and Shab K+ currents to neuronal firing patterns in Drosophila. J Neurophysiol. 2007;97:780-94 pubmed
  42. Webster S, Del Camino D, Dekker J, Yellen G. Intracellular gate opening in Shaker K+ channels defined by high-affinity metal bridges. Nature. 2004;428:864-8 pubmed
    ..A narrower opening of the bundle crossing in Shaker K+ channels may help to explain why Shaker has an approximately tenfold lower conductance than its bacterial relatives. ..
  43. Hackos D, Chang T, Swartz K. Scanning the intracellular S6 activation gate in the shaker K+ channel. J Gen Physiol. 2002;119:521-32 pubmed
    ..Collective examination of the three types of substitutions support the notion that the intracellular portion of S6 forms an activation gate and identifies V478 and F481 as candidates for occlusion of the pore in the closed state. ..
  44. Papazian D, Silverman W, Lin M, Tiwari Woodruff S, Tang C. Structural organization of the voltage sensor in voltage-dependent potassium channels. Novartis Found Symp. 2002;245:178-90; discussion 190-2, 261-4 pubmed
    ..These compatible results from Shaker and eag suggest a model for the packing and conformational changes of transmembrane segments in the voltage sensor of K+ channels. ..
  45. Kashuba V, Kvasha S, Protopopov A, Gizatullin R, Rynditch A, Wahlestedt C, et al. Initial isolation and analysis of the human Kv1.7 (KCNA7) gene, a member of the voltage-gated potassium channel gene family. Gene. 2001;268:115-22 pubmed
    ..Initial comparison to the published murine Kcna7 cDNA suggested a different N-terminal sequence for the human protein, however, further analysis suggests that the original mouse sequence contained an error or an unusual polymorphism. ..
  46. Pongs O, Leicher T, Berger M, Roeper J, Bähring R, Wray D, et al. Functional and molecular aspects of voltage-gated K+ channel beta subunits. Ann N Y Acad Sci. 1999;868:344-55 pubmed
    ..1 subunits leads to a reduction of A-type Kv channel activity in hippocampal and striatal neurons of knock-out mice. This reduction may be correlated with altered cognition and motor control in the knock-out mice. ..
  47. Rodriguez B, Sigg D, Bezanilla F. Voltage gating of Shaker K+ channels. The effect of temperature on ionic and gating currents. J Gen Physiol. 1998;112:223-42 pubmed
  48. Krezel A, Kasibhatla C, Hidalgo P, MacKinnon R, Wagner G. Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry. Protein Sci. 1995;4:1478-89 pubmed
    ..Observed interactions between mutated toxin and channel are being used to elucidate the channel structure and mechanisms of channel-toxin interactions. ..
  49. Laitko U, Juranka P, Morris C. Membrane stretch slows the concerted step prior to opening in a Kv channel. J Gen Physiol. 2006;127:687-701 pubmed
  50. Laitko U, Morris C. Membrane tension accelerates rate-limiting voltage-dependent activation and slow inactivation steps in a Shaker channel. J Gen Physiol. 2004;123:135-54 pubmed
    ..Dynamic structural models of this class of channels will need to take into account the inherent mechanosensitivity of voltage-dependent gating. ..
  51. Laine M, Lin M, Bannister J, Silverman W, Mock A, Roux B, et al. Atomic proximity between S4 segment and pore domain in Shaker potassium channels. Neuron. 2003;39:467-81 pubmed
    ..The model predicts that S4 is located in the groove between pore domains from different subunits, rather than at the periphery of the protein. ..
  52. Lin M, Abramson J, Papazian D. Transfer of ion binding site from ether-a-go-go to Shaker: Mg2+ binds to resting state to modulate channel opening. J Gen Physiol. 2010;135:415-31 pubmed publisher
    ..Comparing our data to the chimera x-ray structure, we conclude that residues in S2 and S3b remain in proximity throughout voltage-dependent activation. ..
  53. McCormack K, Lin L, Sigworth F. Substitution of a hydrophobic residue alters the conformational stability of Shaker K+ channels during gating and assembly. Biophys J. 1993;65:1740-8 pubmed