shab potassium channels


Summary: A subfamily of shaker potassium channels that shares homology with its founding member, Shab protein, Drosophila. They regulate delayed rectifier currents in the NERVOUS SYSTEM of DROSOPHILA and in the SKELETAL MUSCLE and HEART of VERTEBRATES.

Top Publications

  1. Jensen M, Jogini V, Borhani D, Leffler A, Dror R, Shaw D. Mechanism of voltage gating in potassium channels. Science. 2012;336:229-33 pubmed publisher
    ..We propose a mechanistic model for the sodium/potassium/calcium voltage-gated ion channel superfamily that reconciles apparently conflicting experimental data. ..
  2. O Connell K, Tamkun M. Targeting of voltage-gated potassium channel isoforms to distinct cell surface microdomains. J Cell Sci. 2005;118:2155-66 pubmed
    ..1 expressed in HEK cells exhibits a surface distribution similar to that seen in native cells. ..
  3. Ottschytsch N, Raes A, Van Hoorick D, Snyders D. Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome. Proc Natl Acad Sci U S A. 2002;99:7986-91 pubmed
    ..Including the subunits described here, the "silent subunits" represent one-third of all Kv subunits, suggesting that obligatory heterotetramer formation is more widespread than previously thought. ..
  4. MacDonald P, Sewing S, Wang J, Joseph J, Smukler S, Sakellaropoulos G, et al. Inhibition of Kv2.1 voltage-dependent K+ channels in pancreatic beta-cells enhances glucose-dependent insulin secretion. J Biol Chem. 2002;277:44938-45 pubmed
    ..1 is an important component of beta-cell stimulus-secretion coupling, and a compound that enhances, but does not initiate, beta-cell electrical activity by acting on Kv2.1 would be a useful antidiabetic agent. ..
  5. Wei J, Wei L, Zhou X, Lu Z, Francis K, Hu X, et al. Formation of Kv2.1-FAK complex as a mechanism of FAK activation, cell polarization and enhanced motility. J Cell Physiol. 2008;217:544-57 pubmed publisher
    ..1 expression and co-localization of Kv2.1 and FAK significantly enhanced directional cell migration and wound closure. It is suggested that the Kv2.1 channel may function as a promoting signal for FAK activation and cell motility. ..
  6. Andalib P, Wood M, Korn S. Control of outer vestibule dynamics and current magnitude in the Kv2.1 potassium channel. J Gen Physiol. 2002;120:739-55 pubmed
    ..Moreover, the insensitivity of Kv2.1 current magnitude to changes in K+ driving force promotes a more uniform modulation of current over a wide range of membrane potentials by the K+-dependent regulation of outer vestibule conformation...
  7. Feinshreiber L, Singer Lahat D, Friedrich R, Matti U, Sheinin A, Yizhar O, et al. Non-conducting function of the Kv2.1 channel enables it to recruit vesicles for release in neuroendocrine and nerve cells. J Cell Sci. 2010;123:1940-7 pubmed publisher
    ..These findings place a voltage-gated K(+) channel among the syntaxin-binding proteins that directly regulate pre-fusion steps in exocytosis. ..
  8. Mohapatra D, Misonou H, Pan S, Held J, Surmeier D, Trimmer J. Regulation of intrinsic excitability in hippocampal neurons by activity-dependent modulation of the KV2.1 potassium channel. Channels (Austin). 2009;3:46-56 pubmed
    ..1-containing channels. These studies together demonstrate a specific contribution of modulation of KV2.1 channels in the activity-dependent regulation of intrinsic neuronal excitability. ..
  9. Sarmiere P, Weigle C, Tamkun M. The Kv2.1 K+ channel targets to the axon initial segment of hippocampal and cortical neurons in culture and in situ. BMC Neurosci. 2008;9:112 pubmed publisher
    ..Since transfected Kv2.1 initially localizes to the AIS before appearing on the soma, it is likely multiple mechanisms regulate Kv2.1 trafficking to the cell surface. ..

More Information


  1. Bocksteins E, Raes A, Van de Vijver G, Bruyns T, Van Bogaert P, Snyders D. Kv2.1 and silent Kv subunits underlie the delayed rectifier K+ current in cultured small mouse DRG neurons. Am J Physiol Cell Physiol. 2009;296:C1271-8 pubmed publisher
    ..1 channels, whereas the other component represents heterotetrameric K(v)2.1/silent K(v) channels. These observations support a physiological role for silent K(v) subunits in small DRG neurons. ..
  2. Kerschensteiner D, Soto F, Stocker M. Fluorescence measurements reveal stoichiometry of K+ channels formed by modulatory and delayed rectifier alpha-subunits. Proc Natl Acad Sci U S A. 2005;102:6160-5 pubmed
    ..1 subunits and one Kv9.3 subunit. Strikingly, despite this uneven stoichiometry, we find that heteromeric Kv2.1/Kv9.3 channels maintain a pseudosymmetric arrangement of subunits around the central pore. ..
  3. Mankouri J, Dallas M, Hughes M, Griffin S, Macdonald A, Peers C, et al. Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence. Proc Natl Acad Sci U S A. 2009;106:15903-8 pubmed publisher
    ..1. The inhibition of a host cell K(+) channel by a viral protein is a hitherto undescribed viral anti-apoptotic mechanism and represents a potential target for antiviral therapy. ..
  4. Guan D, Horton L, Armstrong W, FOEHRING R. Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons. J Neurophysiol. 2011;105:2976-88 pubmed publisher
    ..The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4-5 wk of age. ..
  5. Immke D, Wood M, Kiss L, Korn S. Potassium-dependent changes in the conformation of the Kv2.1 potassium channel pore. J Gen Physiol. 1999;113:819-36 pubmed
    ..1 was influenced by the conformational rearrangements, either internal to the selectivity filter or near the outer edge of the external vestibule, that were associated with differences in TEA potency. ..
  6. Michaelevski I, Chikvashvili D, Tsuk S, Singer Lahat D, Kang Y, Linial M, et al. Direct interaction of target SNAREs with the Kv2.1 channel. Modal regulation of channel activation and inactivation gating. J Biol Chem. 2003;278:34320-30 pubmed
    ..Based on these results we suggest that exocytosis in neuroendocrine cells is tuned by the dynamic coupling of the Kv2.1 channel gating to the assembly status of the t-SNARE complex. ..
  7. Bocksteins E, Labro A, Mayeur E, Bruyns T, Timmermans J, Adriaensen D, et al. Conserved negative charges in the N-terminal tetramerization domain mediate efficient assembly of Kv2.1 and Kv2.1/Kv6.4 channels. J Biol Chem. 2009;284:31625-34 pubmed publisher
    ..1. These results indicate that these aspartates (especially the first one) in the A/B box linker of the T1 domain are required for efficient assembly of both homotetrameric Kv2.1 and heterotetrameric Kv2.1/silent Kv6.4 channels. ..
  8. Vega Saenz de Miera E. Modification of Kv2.1 K+ currents by the silent Kv10 subunits. Brain Res Mol Brain Res. 2004;123:91-103 pubmed
    ..The gene that encodes for Kv10.1 mRNAs maps to chromosome 2p22.1 in human, 6q12 in rat and 17E4 in mouse, locations consistent with the known systeny for human, rat and mouse chromosomes. ..
  9. Hu X, Wei L, Taylor T, Wei J, Zhou X, Wang J, et al. Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation. Am J Physiol Cell Physiol. 2011;301:C362-72 pubmed publisher
    ..These findings provide novel evidence that HP enhances the ability of BMSCs to migrate and home to the injured region; this effect is mediated through a regulatory role of Kv2.1 on FAK phosphorylation/activation. ..
  10. Johnston J, Griffin S, Baker C, Skrzypiec A, Chernova T, Forsythe I. Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons. J Physiol. 2008;586:3493-509 pubmed publisher
    ..We conclude that Kv2.2-containing channels have a distinctive initial segment location and crucial function in maintaining AP amplitude by regulating the interspike potential during high frequency firing. ..
  11. Cotella D, Hernández Enríquez B, Wu X, Li R, Pan Z, Leveille J, et al. Toxic role of K+ channel oxidation in mammalian brain. J Neurosci. 2012;32:4133-44 pubmed publisher
    ..Together, these data underscore a novel mechanism of toxicity in neurodegenerative disease. ..
  12. Misonou H, Mohapatra D, Menegola M, Trimmer J. Calcium- and metabolic state-dependent modulation of the voltage-dependent Kv2.1 channel regulates neuronal excitability in response to ischemia. J Neurosci. 2005;25:11184-93 pubmed
    ..1 in response to hypoxia/ischemia suppresses neuronal excitability and could confer neuroprotection in response to brief ischemic insults. ..
  13. Mohapatra D, Park K, Trimmer J. Dynamic regulation of the voltage-gated Kv2.1 potassium channel by multisite phosphorylation. Biochem Soc Trans. 2007;35:1064-8 pubmed
    ..1 that is critical to its role as a regulator of intrinsic neuronal excitability. ..
  14. Ramu Y, Xu Y, Lu Z. Enzymatic activation of voltage-gated potassium channels. Nature. 2006;442:696-9 pubmed
    ..Here we report the apparent activation of voltage-gated K+ (Kv) channels by a sphingomyelinase. ..
  15. O Connell K, Rolig A, Whitesell J, Tamkun M. Kv2.1 potassium channels are retained within dynamic cell surface microdomains that are defined by a perimeter fence. J Neurosci. 2006;26:9609-18 pubmed
    ..Channel moves directly into these clusters via trafficking vesicles. Such domains allow for efficient trafficking to the cell surface while sequestering channel with signaling proteins. ..
  16. Jacobson D, Kuznetsov A, Lopez J, Kash S, Ammala C, Philipson L. Kv2.1 ablation alters glucose-induced islet electrical activity, enhancing insulin secretion. Cell Metab. 2007;6:229-35 pubmed
    ..These results reveal the specific role of Kv2.1 in modulating glucose-stimulated APs of beta cells, exposing additional important currents involved in regulating physiological insulin secretion. ..
  17. Mohapatra D, Trimmer J. The Kv2.1 C terminus can autonomously transfer Kv2.1-like phosphorylation-dependent localization, voltage-dependent gating, and muscarinic modulation to diverse Kv channels. J Neurosci. 2006;26:685-95 pubmed
    ..1 channel by cholinergic and other neuromodulatory stimuli. ..
  18. Pal S, Takimoto K, Aizenman E, Levitan E. Apoptotic surface delivery of K+ channels. Cell Death Differ. 2006;13:661-7 pubmed
    ..These data indicate that trafficking of Kv2.1 channels to the plasma membrane causes the apoptotic surge in K+ current. ..
  19. Shepherd A, Loo L, Gupte R, Mickle A, Mohapatra D. Distinct modifications in Kv2.1 channel via chemokine receptor CXCR4 regulate neuronal survival-death dynamics. J Neurosci. 2012;32:17725-39 pubmed publisher
    ..1 in response to short- and long-term CXCR4-mediated signaling could provide a basis for neuroprotection or apoptosis in neuropathologies, such as neuroinflammation, stroke, brain tumors, and HIV-associated neurodegeneration. ..
  20. He Y, Zhan X, Yang G, Sun J, Mei Y. Amoxapine inhibits the delayed rectifier outward K+ current in mouse cortical neurons via cAMP/protein kinase A pathways. J Pharmacol Exp Ther. 2010;332:437-45 pubmed publisher
    ..Together these results suggest that amoxapine inhibits I(K) in mouse cortical neurons by cAMP/PKA-dependent pathway associated with the 5-HT receptor, and suggest that the Kv2.1 alpha-subunit may be the target for this inhibition. ..
  21. Kihira Y, Hermanstyne T, Misonou H. Formation of heteromeric Kv2 channels in mammalian brain neurons. J Biol Chem. 2010;285:15048-55 pubmed publisher
    ..Our results suggest that the delayed rectifier currents, which regulate action potential firing, are encoded by heteromeric Kv2 channels in cortical neurons. ..
  22. Weigel A, Simon B, Tamkun M, Krapf D. Ergodic and nonergodic processes coexist in the plasma membrane as observed by single-molecule tracking. Proc Natl Acad Sci U S A. 2011;108:6438-43 pubmed publisher
    ..1 channels recovers ergodicity. However, the fractal structure that induces anomalous diffusion remains unaltered. These results have direct implications on the regulation of membrane receptor trafficking and signaling. ..
  23. Ikematsu N, Dallas M, Ross F, Lewis R, Rafferty J, David J, et al. Phosphorylation of the voltage-gated potassium channel Kv2.1 by AMP-activated protein kinase regulates membrane excitability. Proc Natl Acad Sci U S A. 2011;108:18132-7 pubmed publisher
    ..Our results suggest that activation of AMPK in neurons during conditions of metabolic stress exerts a protective role by reducing neuronal excitability and thus conserving energy. ..
  24. Butler A, Wei A, Baker K, Salkoff L. A family of putative potassium channel genes in Drosophila. Science. 1989;243:943-7 pubmed
    ..Thus, potassium channel diversity could result from an extended gene family, as well as from alternate splicing of the Shaker primary transcript. ..
  25. MacDonald P, Wang G, Tsuk S, Dodo C, Kang Y, Tang L, et al. Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-dependent K(+) channels in neuroendocrine islet beta-cells through an interaction with the channel N terminus. Mol Endocrinol. 2002;16:2452-61 pubmed
    ..1 through an interaction at the channel N terminus and supports the hypothesis that SNARE proteins modulate secretion through their involvement in regulation of membrane ion channels in addition to exocytic membrane fusion. ..
  26. Park K, Mohapatra D, Misonou H, Trimmer J. Graded regulation of the Kv2.1 potassium channel by variable phosphorylation. Science. 2006;313:976-9 pubmed
    ..Mutations at multiple sites were additive, showing that variable phosphorylation of Kv2.1 at a large number of sites allows graded activity-dependent regulation of channel gating and neuronal firing properties. ..
  27. Wolf Goldberg T, Michaelevski I, Sheu L, Gaisano H, Chikvashvili D, Lotan I. Target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (t-SNAREs) differently regulate activation and inactivation gating of Kv2.2 and Kv2.1: Implications on pancreatic islet cell Kv channels. Mol Pharmacol. 2006;70:818-28 pubmed
  28. Amberg G, Santana L. Kv2 channels oppose myogenic constriction of rat cerebral arteries. Am J Physiol Cell Physiol. 2006;291:C348-56 pubmed
  29. Misonou H, Mohapatra D, Trimmer J. Kv2.1: a voltage-gated k+ channel critical to dynamic control of neuronal excitability. Neurotoxicology. 2005;26:743-52 pubmed
    ..1 localization and function in neurons, and summarize recent work regarding dynamic regulation of these characteristics. We also discuss possible roles of the Kv2.1 channel in neuronal and network excitability. ..
  30. Dallas M, Boyle J, Milligan C, Sayer R, Kerrigan T, McKinstry C, et al. Carbon monoxide protects against oxidant-induced apoptosis via inhibition of Kv2.1. FASEB J. 2011;25:1519-30 pubmed publisher
    ..Our results provide a novel mechanism to account for the neuroprotective effects of CO against oxidative apoptosis, which has potential for therapeutic exploitation to provide neuronal protection in situations of oxidative stress. ..
  31. Weigel A, Tamkun M, Krapf D. Anomalous diffusion of kv2.1 channels observed by single molecule tracking in live cells. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:3005-8 pubmed publisher
    ..The effect of actin cytoskeleton on the diffusion properties of the channels is also investigated in the presence of cytochalasin D, a F-actin binding drug that blocks actin polymerization. ..
  32. Deutsch E, Weigel A, Akin E, Fox P, Hansen G, Haberkorn C, et al. Kv2.1 cell surface clusters are insertion platforms for ion channel delivery to the plasma membrane. Mol Biol Cell. 2012;23:2917-29 pubmed publisher
    ..These results indicate that one nonconducting function of Kv2.1 is to form microdomains involved in membrane protein trafficking. This study is the first to identify stable cell surface platforms involved in ion channel trafficking. ..
  33. Consiglio J, Andalib P, Korn S. Influence of pore residues on permeation properties in the Kv2.1 potassium channel. Evidence for a selective functional interaction of K+ with the outer vestibule. J Gen Physiol. 2003;121:111-24 pubmed
    ..We discuss the implications of these findings in relation to the structural basis of channel conductance in different K(+) channels. ..
  34. Klemic K, Shieh C, Kirsch G, Jones S. Inactivation of Kv2.1 potassium channels. Biophys J. 1998;74:1779-89 pubmed
    ..quot; These results can be explained by an allosteric model, in which inactivation is favored by activation of voltage sensors, but the open state of the channel is resistant to inactivation. ..
  35. Consiglio J, Korn S. Influence of permeant ions on voltage sensor function in the Kv2.1 potassium channel. J Gen Physiol. 2004;123:387-400 pubmed
    ..These results provide strong evidence for a direct functional interaction, which is modulated by permeant ions acting at the selectivity filter, between the outer vestibule of the Kv2.1 potassium channel and the voltage sensor. ..
  36. Murakoshi H, Shi G, Scannevin R, Trimmer J. Phosphorylation of the Kv2.1 K+ channel alters voltage-dependent activation. Mol Pharmacol. 1997;52:821-8 pubmed
    ..1 can be modulated by direct phosphorylation of the channel protein; such modulation of Kv2.1 could dynamically regulate dendritic excitability. ..
  37. Ryan M, Maloney R, Reenan R, Horn R. Characterization of five RNA editing sites in Shab potassium channels. Channels (Austin). 2008;2:202-9 pubmed
    ..These results show that both the position of the RNA editing site and the identity of the substituted amino acid are important for channel function. ..
  38. Mulholland P, Carpenter Hyland E, Hearing M, Becker H, Woodward J, Chandler L. Glutamate transporters regulate extrasynaptic NMDA receptor modulation of Kv2.1 potassium channels. J Neurosci. 2008;28:8801-9 pubmed publisher
    ..These data support a novel mechanism for glutamate transporters in regulation of neuronal excitability and plasticity through extrasynaptic NMDA receptor modulation of Kv2.1 channels. ..
  39. Hwang P, Glatt C, Bredt D, Yellen G, Snyder S. A novel K+ channel with unique localizations in mammalian brain: molecular cloning and characterization. Neuron. 1992;8:473-81 pubmed
    ..In peripheral tissues, mRNAs for cdrk and drk1 are reciprocally localized, indicating that the K+ channel properties contributed by mammalian Shab homologs may be important in a variety of excitable tissues. ..
  40. Al Owais M, Scragg J, Dallas M, Boycott H, Warburton P, Chakrabarty A, et al. Carbon monoxide mediates the anti-apoptotic effects of heme oxygenase-1 in medulloblastoma DAOY cells via K+ channel inhibition. J Biol Chem. 2012;287:24754-64 pubmed publisher
  41. Frech G, VanDongen A, Schuster G, Brown A, Joho R. A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning. Nature. 1989;340:642-5 pubmed
    ..The channels show sigmoidal voltage-dependent activation and do not inactivate within 500 ms. Structurally, drk1 encodes an amino-acid sequence which is more closely related to the Drosophila Shab gene than to the Shaker gene. ..
  42. Misonou H, Mohapatra D, Park E, Leung V, Zhen D, Misonou K, et al. Regulation of ion channel localization and phosphorylation by neuronal activity. Nat Neurosci. 2004;7:711-8 pubmed
    ..Our finding that neuronal activity modifies the phosphorylation state, localization and function of Kv2.1 suggests an important link between excitatory neurotransmission and the intrinsic excitability of pyramidal neurons. ..
  43. Wu X, Hernández Enríquez B, Banas M, Xu R, Sesti F. Molecular mechanisms underlying the apoptotic effect of KCNB1 K+ channel oxidation. J Biol Chem. 2013;288:4128-34 pubmed publisher
    ..Together, these data suggest that the accumulation of KCNB1 oligomers in the membrane disrupts planar lipid raft integrity and causes apoptosis via activating the c-Src/JNK signaling pathway. ..
  44. Mohapatra D, Siino D, Trimmer J. Interdomain cytoplasmic interactions govern the intracellular trafficking, gating, and modulation of the Kv2.1 channel. J Neurosci. 2008;28:4982-94 pubmed publisher
    ..1 trafficking, gating, and phosphorylation-dependent modulation through cytoplasmic N/C-terminal interaction, which resembles alpha/beta subunit interaction in other Kv channels. ..
  45. Thibault K, Calvino B, Dubacq S, Roualle de Rouville M, Sordoillet V, Rivals I, et al. Cortical effect of oxaliplatin associated with sustained neuropathic pain: exacerbation of cortical activity and down-regulation of potassium channel expression in somatosensory cortex. Pain. 2012;153:1636-47 pubmed publisher
  46. McCord M, Aizenman E. Convergent Ca2+ and Zn2+ signaling regulates apoptotic Kv2.1 K+ currents. Proc Natl Acad Sci U S A. 2013;110:13988-93 pubmed publisher
  47. Roe M, Worley J, Mittal A, Kuznetsov A, DasGupta S, Mertz R, et al. Expression and function of pancreatic beta-cell delayed rectifier K+ channels. Role in stimulus-secretion coupling. J Biol Chem. 1996;271:32241-6 pubmed
    ..These studies implicate previously uncharacterized beta-cell delayed rectifier K+ channels in the regulation of membrane repolarization, [Ca2+]i, and insulin secretion. ..
  48. Song M, Hong C, Bae S, So I, Park K. Dynamic modulation of the kv2.1 channel by SRC-dependent tyrosine phosphorylation. J Proteome Res. 2012;11:1018-26 pubmed publisher
    ..1 are crucial to regulating diverse aspects of Kv2.1 channel function and provide novel insights into molecular mechanisms for the regulation of Src-dependent modulation of Kv2.1 channels. ..
  49. Malin S, Nerbonne J. Delayed rectifier K+ currents, IK, are encoded by Kv2 alpha-subunits and regulate tonic firing in mammalian sympathetic neurons. J Neurosci. 2002;22:10094-105 pubmed
    ..Expression of Kv2.2DN also results in membrane depolarization, suggesting that Kv2.1- and Kv2.2-encoded I(K) channels play distinct roles in regulating the excitability of SCG neurons. ..
  50. Lee C, Kim S, Roh S, Endoh H, Kodera Y, Maeda T, et al. Solution structure and functional characterization of SGTx1, a modifier of Kv2.1 channel gating. Biochemistry. 2004;43:890-7 pubmed
  51. Dai X, Kolic J, Marchi P, Sipione S, MacDonald P. SUMOylation regulates Kv2.1 and modulates pancreatic beta-cell excitability. J Cell Sci. 2009;122:775-9 pubmed publisher
    ..Thus, protein SUMOylation can exert a strong inhibitory action on the voltage-dependent K(+) channel Kv2.1 and can regulate cellular excitability in native beta-cells. ..
  52. Singer Lahat D, Sheinin A, Chikvashvili D, Tsuk S, Greitzer D, Friedrich R, et al. K+ channel facilitation of exocytosis by dynamic interaction with syntaxin. J Neurosci. 2007;27:1651-8 pubmed
  53. Escoubas P, Diochot S, Célérier M, Nakajima T, Lazdunski M. Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies. Mol Pharmacol. 2002;62:48-57 pubmed
    ..HmTx1 is the first described peptide effector of the Kv4.1 subtype. Those novel toxins are new tools for the investigation of the physiological role of the different potassium channel subunits in cellular physiology. ..