Kcna2

Summary

Gene Symbol: Kcna2
Description: potassium voltage-gated channel subfamily A member 2
Alias: BK2, NGK1, potassium voltage-gated channel subfamily A member 2, Potassium (K+) channel protein alpha 2, voltage dependent, Potassium voltage gated channel shaker related subfamily member 2, RAK, RBK2, RCK5, potassium channel, voltage gated shaker related subfamily A, member 2, potassium voltage-gated channel, shaker-related subfamily, member 2, voltage-gated potassium channel subunit Kv1.2
Species: rat
Products:     Kcna2

Top Publications

  1. Rivera J, Chu P, Lewis T, Arnold D. The role of Kif5B in axonal localization of Kv1 K(+) channels. Eur J Neurosci. 2007;25:136-46 pubmed
    ..Together these data suggest a model where Kif5B interacts with Kv1 channels either directly or indirectly via the T1 domain, causing the channels to be transported to axons. ..
  2. Shi G, Nakahira K, Hammond S, Rhodes K, Schechter L, Trimmer J. Beta subunits promote K+ channel surface expression through effects early in biosynthesis. Neuron. 1996;16:843-52 pubmed
    ..These findings provide a molecular basis for recent genetic studies indicating that beta subunits are key determinants of neuronal excitability. ..
  3. Rhodes K, Strassle B, Monaghan M, Bekele Arcuri Z, Matos M, Trimmer J. Association and colocalization of the Kvbeta1 and Kvbeta2 beta-subunits with Kv1 alpha-subunits in mammalian brain K+ channel complexes. J Neurosci. 1997;17:8246-58 pubmed
  4. Poliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer J, et al. Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron. 1999;24:1037-47 pubmed
    ..This association involves the C-terminal sequence of Caspr2, which contains a putative PDZ binding site. These results suggest a role for Caspr family members in the local differentiation of the axon into distinct functional subdomains. ..
  5. Tao X, MacKinnon R. Functional analysis of Kv1.2 and paddle chimera Kv channels in planar lipid bilayers. J Mol Biol. 2008;382:24-33 pubmed publisher
    ..2. We find, however, that in several respects, the Kv1.2 channel exhibits functional properties that are distinct from Kv1.2 channels reported in the literature. ..
  6. Fulton S, Thibault D, Mendez J, Lahaie N, Tirotta E, Borrelli E, et al. Contribution of Kv1.2 voltage-gated potassium channel to D2 autoreceptor regulation of axonal dopamine overflow. J Biol Chem. 2011;286:9360-72 pubmed publisher
    ..2-containing channels in striatal tissue. These findings underline the contribution of Kv1.2 in the regulation of nigrostriatal DA release by the D2-AR and thereby offer a novel mechanism by which DA release is regulated. ..
  7. Long S, Campbell E, MacKinnon R. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science. 2005;309:897-903 pubmed
    ..Electrostatic properties of the side portals and positions of the T1 domain and beta subunit are consistent with electrophysiological studies of inactivation gating and with the possibility of K+ channel regulation by the beta subunit. ..
  8. Zhao X, Tang Z, Zhang H, Atianjoh F, Zhao J, Liang L, et al. A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons. Nat Neurosci. 2013;16:1024-31 pubmed publisher
    ..Here we identify a conserved lncRNA, named Kcna2 antisense RNA, for a voltage-dependent potassium channel mRNA, Kcna2, in first-order sensory neurons of rat dorsal ..
  9. Chen X, Wang Q, Ni F, Ma J. Structure of the full-length Shaker potassium channel Kv1.2 by normal-mode-based X-ray crystallographic refinement. Proc Natl Acad Sci U S A. 2010;107:11352-7 pubmed publisher
    ..2 between the internal and external solutions. This work also demonstrated the potential of the refinement method in bringing up large chunks of missing densities, thus beneficial to structural refinement of many difficult systems. ..

More Information

Publications56

  1. Douglas C, Vyazovskiy V, Southard T, Chiu S, Messing A, Tononi G, et al. Sleep in Kcna2 knockout mice. BMC Biol. 2007;5:42 pubmed
    ..To address this issue, we studied sleep in Kcna2 knockout (KO) mice. Kcna2 codes for Kv1...
  2. Cordero Morales J, Jogini V, Lewis A, Vásquez V, Cortes D, Roux B, et al. Molecular driving forces determining potassium channel slow inactivation. Nat Struct Mol Biol. 2007;14:1062-9 pubmed
    ..2 suggests that a similar mechanistic principle applies to other K+ channels. These observations provide a plausible physical framework for understanding C-type inactivation in K+ channels. ..
  3. Fujita T, Utsunomiya I, Ren J, Matsushita Y, Kawai M, Sasaki S, et al. Glycosylation and cell surface expression of Kv1.2 potassium channel are regulated by determinants in the pore region. Neurochem Res. 2006;31:589-96 pubmed
    ..2 and cells coexpressing beta2and S360A. These results suggest that amino acids in the pore region help regulate ion permeability or cellular trafficking by affecting glycosylation of Kv1.2. ..
  4. Finnegan T, Chen S, Pan H. Mu opioid receptor activation inhibits GABAergic inputs to basolateral amygdala neurons through Kv1.1/1.2 channels. J Neurophysiol. 2006;95:2032-41 pubmed
    ..This study provides new information that activation of presynaptic mu opioid receptors primarily attenuates GABAergic synaptic inputs to CeA-projecting neurons in the BLA through a signaling mechanism involving Kv1.1 and Kv1.2 channels. ..
  5. Al Sabi A, Kaza S, Dolly J, Wang J. Pharmacological characteristics of Kv1.1- and Kv1.2-containing channels are influenced by the stoichiometry and positioning of their ? subunits. Biochem J. 2013;454:101-8 pubmed publisher
    ..This is important in designing drugs with abilities to inhibit particular oligomeric Kv1 subtypes, with the goal of elevating neuronal excitability and improving neurotransmission in certain diseases. ..
  6. Hattan D, Nesti E, Cachero T, Morielli A. Tyrosine phosphorylation of Kv1.2 modulates its interaction with the actin-binding protein cortactin. J Biol Chem. 2002;277:38596-606 pubmed
    ..These results demonstrate a dynamic, phosphorylation-dependent interaction between Kv1.2 and the actin cytoskeleton-binding protein cortactin and suggest a role for that interaction in the regulation of Kv1.2 ionic current. ..
  7. 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
  8. Li F, Lu J, Wu C, Kaur C, Sivakumar V, Sun J, et al. Expression of Kv1.2 in microglia and its putative roles in modulating production of proinflammatory cytokines and reactive oxygen species. J Neurochem. 2008;106:2093-105 pubmed publisher
    ..We conclude that Kv1.2 in microglia modulates IL-1beta and TNF-alpha expression and ROS production probably by regulating the intracellular potassium concentration. ..
  9. Kuryshev Y, Wible B, Gudz T, Ramirez A, Brown A. KChAP/Kvbeta1.2 interactions and their effects on cardiac Kv channel expression. Am J Physiol Cell Physiol. 2001;281:C290-9 pubmed
    ..2 may alter both sustained and transient cardiac Kv currents. The interaction of these two different classes of modulatory proteins may constitute a novel mechanism for regulating cardiac K+ currents...
  10. Hyun J, Eom K, Lee K, Bae J, Bae Y, Kim M, et al. Kv1.2 mediates heterosynaptic modulation of direct cortical synaptic inputs in CA3 pyramidal cells. J Physiol. 2015;593:3617-43 pubmed publisher
    ..These results indicate that activity-dependent downregulation of Kv1.2 in CA3-PCs mediates MF-induced heterosynaptic LTP of PP-EPSPs by facilitating activation of Na(+) channels at distal apical dendrites. ..
  11. Zhao L, Wu A, Bi L, Liu P, Zhang X, Jiang T, et al. Length-dependent regulation of the Kv1.2 channel activation by its C-terminus. Mol Membr Biol. 2009;26:186-93 pubmed publisher
    ..2 channel. These results imply that the dynamic interaction of the C-terminus with the S4-S5 linker from a neighboring subunit of the Kv1.2 channel provides a mechanism for its C-terminus to regulate the channel activation. ..
  12. Chai Q, Xu X, Jia Q, Dong Q, Liu Z, Zhang W, et al. Molecular basis of dysfunctional Kv channels in small coronary artery smooth muscle cells of streptozotocin-induced diabetic rats. Chin J Physiol. 2007;50:171-7 pubmed
  13. Peters C, Vaid M, Horne A, Fedida D, Accili E. The molecular basis for the actions of KVbeta1.2 on the opening and closing of the KV1.2 delayed rectifier channel. Channels (Austin). 2009;3:314-22 pubmed
    ..Together with data from previous studies, our findings provide a complete and coherent picture of the functional and structural interactions between K(V)beta1.2 and K(V)1.2. ..
  14. Ramaswami M, Gautam M, Kamb A, Rudy B, Tanouye M, Mathew M. Human potassium channel genes: Molecular cloning and functional expression. Mol Cell Neurosci. 1990;1:214-23 pubmed
    ..Differences are observed between the pharmacological sensitivities of human channels and the reported sensitivities of their rat homology. ..
  15. Gu Y, Gu C. Dynamics of Kv1 channel transport in axons. PLoS ONE. 2010;5:e11931 pubmed publisher
    ..2 tetramers in axonal puncta. Taken together, our results suggest that proper amounts of Kv1 channels and their associated proteins are required for efficient transport of Kv1 channel proteins along axons. ..
  16. Zhao L, Qi Z, Zhang X, Bi L, Jin G. Regulatory role of the extreme C-terminal end of the S6 inner helix in C-terminal-truncated Kv1.2 channel activation. Cell Biol Int. 2010;34:433-9 pubmed publisher
    ..Hence, our results indicate that the extreme C-terminal end of the S6 inner helix plays an important regulatory role in the activation of the C-terminal-truncated Kv1.2 channel. ..
  17. Stuhmer W, Ruppersberg J, Schröter K, Sakmann B, Stocker M, Giese K, et al. Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. EMBO J. 1989;8:3235-44 pubmed
  18. Bubolz A, Wu Q, Larsen B, Gutterman D, Liu Y. Ebselen reduces nitration and restores voltage-gated potassium channel function in small coronary arteries of diabetic rats. Am J Physiol Heart Circ Physiol. 2007;293:H2231-7 pubmed
    ..Eb may be beneficial for the therapeutic treatment of vascular complications in diabetes mellitus. ..
  19. Lu Y, Hanna S, Tang G, Wang R. Contributions of Kv1.2, Kv1.5 and Kv2.1 subunits to the native delayed rectifier K(+) current in rat mesenteric artery smooth muscle cells. Life Sci. 2002;71:1465-73 pubmed
    ..A control antibody (anti-GIRK1) also had no effect on the native Kv currents. This study demonstrates that Kv1.2, Kv1.5, and Kv2.1 subunit genes all contribute to the formation of the native Kv channels in rat mesenteric artery SMCs. ..
  20. Paulmichl M, Nasmith P, Hellmiss R, Reed K, Boyle W, Nerbonne J, et al. Cloning and expression of a rat cardiac delayed rectifier potassium channel. Proc Natl Acad Sci U S A. 1991;88:7892-5 pubmed
    We have cloned a cDNA (designated RAK) coding for a delayed-rectifier K current (IRAK) from adult rat heart atrium and expressed it in Xenopus oocytes. RAK differs from the cloned rat brain K current, BK2 [McKinnon, D. (1989) J. Biol...
  21. McKinnon D. Isolation of a cDNA clone coding for a putative second potassium channel indicates the existence of a gene family. J Biol Chem. 1989;264:8230-6 pubmed
    ..This new potassium channel is called BK2 to distinguish it from the previously described potassium channel (BK1)...
  22. Williams M, Fuchs J, Green J, Morielli A. Cellular mechanisms and behavioral consequences of Kv1.2 regulation in the rat cerebellum. J Neurosci. 2012;32:9228-37 pubmed publisher
    ..2 endocytosis is supported by our finding that infusion into the cerebellar cortex of either the Kv1.2 inhibitor tityustoxin-K?, or of the Kv1.2 regulator secretin, significantly enhances acquisition of eyeblink conditioning in rats. ..
  23. Banerjee A, Lee A, CAMPBELL E, MacKinnon R. Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K(+) channel. elife. 2013;2:e00594 pubmed publisher
    ..Together, these results show that CTX binds to a K(+) channel in a lock and key manner and interacts directly with conducting ions inside the selectivity filter. DOI:http://dx.doi.org/10.7554/eLife.00594.001. ..
  24. Fan L, Guan X, Wang W, Zhao J, Zhang H, Tiwari V, et al. Impaired neuropathic pain and preserved acute pain in rats overexpressing voltage-gated potassium channel subunit Kv1.2 in primary afferent neurons. Mol Pain. 2014;10:8 pubmed publisher
    ..2 antisense RNA, in addition to the increase in Kv1.2 protein expression, in the injured DRG. Our findings suggest that Kv1.2 may be a novel potential target for preventing and/or treating neuropathic pain. ..
  25. Dodson P, Barker M, Forsythe I. Two heteromeric Kv1 potassium channels differentially regulate action potential firing. J Neurosci. 2002;22:6953-61 pubmed
    ..Our results show that heteromeric channels containing Kv1.2 subunits govern AP firing and suggest that their localization at the initial segment of MNTB axons can explain their dominance of AP firing behavior. ..
  26. Minor D, Lin Y, Mobley B, Avelar A, Jan Y, Jan L, et al. The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel. Cell. 2000;102:657-70 pubmed
    ..Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening. ..
  27. Jensen M, Borhani D, Lindorff Larsen K, Maragakis P, Jogini V, Eastwood M, et al. Principles of conduction and hydrophobic gating in K+ channels. Proc Natl Acad Sci U S A. 2010;107:5833-8 pubmed publisher
  28. Wang H, Kunkel D, Schwartzkroin P, Tempel B. Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain. J Neurosci. 1994;14:4588-99 pubmed
    ..This overlapping yet differential pattern of expression and specific subcellular localization may contribute to the unique profile of excitability displayed by a particular neuron. ..
  29. Kasahara K, Shirota M, Kinoshita K. Ion Concentration- and Voltage-Dependent Push and Pull Mechanisms of Potassium Channel Ion Conduction. PLoS ONE. 2016;11:e0150716 pubmed publisher
  30. Kim E, Niethammer M, Rothschild A, Jan Y, Sheng M. Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature. 1995;378:85-8 pubmed
    ..3) and syntrophin), suggest that PDZ-domain-containing polypeptides may be widely involved in the organization of proteins at sites of membrane specialization. ..
  31. Yang J, Vacher H, Park K, Clark E, Trimmer J. Trafficking-dependent phosphorylation of Kv1.2 regulates voltage-gated potassium channel cell surface expression. Proc Natl Acad Sci U S A. 2007;104:20055-60 pubmed
    ..These data support Kv1.2 phosphorylation at these clustered C-terminal sites as playing an important role in regulating trafficking of Kv1.2-containing Kv channels. ..
  32. Dodson P, Billups B, Rusznák Z, Szucs G, Barker M, Forsythe I. Presynaptic rat Kv1.2 channels suppress synaptic terminal hyperexcitability following action potential invasion. J Physiol. 2003;550:27-33 pubmed
    ..We conclude that Kv1.2 channels have a general presynaptic function in suppressing terminal hyperexcitability during the depolarising after-potential. ..
  33. Traka M, Goutebroze L, Denisenko N, Bessa M, Nifli A, Havaki S, et al. Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers. J Cell Biol. 2003;162:1161-72 pubmed
    ..This complex is analogous to that described previously at paranodes, suggesting that similar molecules are crucial for different types of axo-glial interactions. ..
  34. Ogawa Y, Oses Prieto J, Kim M, Horresh I, Peles E, Burlingame A, et al. ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated guanylate kinases to juxtaparanodes of myelinated axons. J Neurosci. 2010;30:1038-48 pubmed publisher
    ..2 and Caspr2 clustering is normal in ADAM22-null mice. Thus, ADAM22 is an axonal component of the Kv1 K(+) channel complex that recruits MAGUKs to juxtaparanodes. ..
  35. Chen C, Westenbroek R, Xu X, Edwards C, Sorenson D, Chen Y, et al. Mice lacking sodium channel beta1 subunits display defects in neuronal excitability, sodium channel expression, and nodal architecture. J Neurosci. 2004;24:4030-42 pubmed
  36. Li Z, Lu N, Shi L. Exercise training reverses alterations in Kv and BKCa channel molecular expression in thoracic aorta smooth muscle cells from spontaneously hypertensive rats. J Vasc Res. 2014;51:447-57 pubmed publisher
    ..These data suggest that exercise training reverses the pathological expression of the Kv1.2, Kv1.5, and BKCa channels in aortic myocytes from SHRs. This is one of the favorable effects of exercise training on large conduit arteries. ..
  37. Kariev A, Green M. Caution is required in interpretation of mutations in the voltage sensing domain of voltage gated channels as evidence for gating mechanisms. Int J Mol Sci. 2015;16:1627-43 pubmed publisher
    ..The computations strongly suggest that the interpretation of cysteine substitution reaction experiments be re-examined in the light of these considerations. ..
  38. Gordon A, Adamsky K, Vainshtein A, Frechter S, Dupree J, Rosenbluth J, et al. Caspr and caspr2 are required for both radial and longitudinal organization of myelinated axons. J Neurosci. 2014;34:14820-6 pubmed publisher
    ..Our results indicate that Caspr and Caspr2 are required for the organization of the axolemma both radially, manifested as the mesaxonal line, and longitudinally, demarcated by the nodal domains. ..
  39. Caminos E, Vale C, Lujan R, Martinez Galan J, Juiz J. Developmental regulation and adult maintenance of potassium channel proteins (Kv 1.1 and Kv 1.2) in the cochlear nucleus of the rat. Brain Res. 2005;1056:118-31 pubmed
    ..Thus, normal excitatory synaptic input in adult animals is not a requirement to regulate the expression and cellular and subcellular distribution of these potassium channel proteins. ..
  40. Pan Z, Kao T, Horvath Z, Lemos J, Sul J, Cranstoun S, et al. A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon. J Neurosci. 2006;26:2599-613 pubmed
    ..This includes the historical period when myelin also evolved. ..
  41. Lewis A, Jogini V, Blachowicz L, Laine M, Roux B. Atomic constraints between the voltage sensor and the pore domain in a voltage-gated K+ channel of known structure. J Gen Physiol. 2008;131:549-61 pubmed publisher
    ..2 x-ray structure. A structural model is provided for this conformation. The results further highlight the dynamic and flexible nature of the voltage sensor. ..
  42. Gu C, Gu Y. Clustering and activity tuning of Kv1 channels in myelinated hippocampal axons. J Biol Chem. 2011;286:25835-47 pubmed publisher
    ..This effect was eliminated by the Tyr??? mutation or by cholesterol depletion. Taken together, our studies suggest that myelin regulates both trafficking and activity of Kv1 channels along hippocampal axons through TAG-1. ..
  43. Al Sabi A, Shamotienko O, Dhochartaigh S, Muniyappa N, Le Berre M, Shaban H, et al. Arrangement of Kv1 alpha subunits dictates sensitivity to tetraethylammonium. J Gen Physiol. 2010;136:273-82 pubmed publisher
    ..These collective findings indicate that assembly of alpha subunits can be directed by this optimized concatenation, and that subunit arrangement in heteromeric Kv channels affects TEA affinity...
  44. Cox R, Fromme S, Folander K, Swanson R. Voltage gated K+ channel expression in arteries of Wistar-Kyoto and spontaneously hypertensive rats. Am J Hypertens. 2008;21:213-8 pubmed publisher
    ..The higher expression of K(v) subunits in small mesenteric arteries (SMAs) of SHR would tend to maintain normal myogenic activity and vasoconstrictor reserve, and could be viewed as a form of homeostatic remodeling. ..
  45. Rasband M, Trimmer J. Subunit composition and novel localization of K+ channels in spinal cord. J Comp Neurol. 2001;429:166-76 pubmed
    ..Moreover, the conservation of these characteristics between human, rat, and bovine nodes of Ranvier suggests an essential role for this defined channel complex in spinal cord function. ..
  46. Jensen K, Brandt S, Shigematsu H, Sigworth F. Statistical modeling and removal of lipid membrane projections for cryo-EM structure determination of reconstituted membrane proteins. J Struct Biol. 2016;194:49-60 pubmed publisher
    ..Precise removal of the strong membrane signals allows better alignment and classification of images of small membrane-protein particles, and allows higher-resolution 3D reconstruction. ..
  47. Savvaki M, Panagiotaropoulos T, Stamatakis A, Sargiannidou I, Karatzioula P, Watanabe K, et al. Impairment of learning and memory in TAG-1 deficient mice associated with shorter CNS internodes and disrupted juxtaparanodes. Mol Cell Neurosci. 2008;39:478-90 pubmed publisher
    ..Moreover, Tag-1(-/-) mice had shorter internodes in the cerebral and cerebellar white matter. The detected molecular alterations may account for the behavioural deficits and hyperexcitability in these animals. ..