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PMID: 10454353 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Reduced K+ channel inactivation, spike broadening, and after-hyperpolarization in Kvbeta1.1-deficient mice with impaired learning.

Learning & memory (Cold Spring Harbor, N.Y.) ·Vol. 5 ·No. 4-5 ·1998-00-00 ·Pages 257-73

Giese KP, Storm JF, Reuter D, Fedorov NB, Shao LR, Leicher T, Pongs O, Silva AJ

Abstract

A-type K+ channels are known to regulate neuronal firing, but their role in repetitive firing and learning in mammals is not well characterized. To determine the contribution of the auxiliary K+ channel subunit Kvbeta1.1 to A-type K+ currents and to study the physiological role of A-type K+ channels in repetitive firing and learning, we deleted the Kvbeta1.1 gene in mice. The loss of Kvbeta1.1 resulted in a reduced K+ current inactivation in hippocampal CA1 pyramidal neurons. Furthermore, in the mutant neurons, frequency-dependent spike broadening and the slow afterhyperpolarization (sAHP) were reduced. This suggests that Kvbeta1.1-dependent A-type K+ channels contribute to frequency-dependent spike broadening and may regulate the sAHP by controlling Ca2+ influx during action potentials. The Kvbeta1.1-deficient mice showed normal synaptic plasticity but were impaired in the learning of a water maze test and in the social transmission of food preference task, indicating that the Kvbeta1.1 subunit contributes to certain types of learning and memory.

MeSH Terms
Action Potentials/physiology Animals Calcium/physiology Cues Evoked Potentials/physiology Food Preferences Hippocampus/pathology,physiology,physiopathology Kv1.1 Potassium Channel Kv1.3 Potassium Channel Large-Conductance Calcium-Activated Potassium Channel beta Subunits Learning Disabilities/genetics,pathology,physiopathology Maze Learning/physiology Mice Mice, Knockout Neuronal Plasticity Potassium Channels/deficiency,genetics,physiology Potassium Channels, Voltage-Gated Pyramidal Cells/pathology,physiology Social Behavior Synapses/physiology
Chemicals
Kcna1 protein, mouse Kcnab1 protein, mouse Kv1.3 Potassium Channel Large-Conductance Calcium-Activated Potassium Channel beta Subunits Potassium Channels Potassium Channels, Voltage-Gated Kv1.1 Potassium Channel Calcium
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Giese K P
Cold Spring Harbor Laboratory, New York 11724, USA.
Storm J F
Reuter D
Fedorov N B
Shao L R
Leicher T
Pongs O
Silva A J
References (72)
72 references, click to expand
  1. Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB.
    Science. 1990 Oct 26;250(4980):568-71 PMID: 2122520
  2. Primary structure of a beta subunit of alpha-dendrotoxin-sensitive K+ channels from bovine brain.
    Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1637-41 PMID: 8127858
  3. Mechanism of frequency-dependent broadening of molluscan neurone soma spikes.
    J Physiol. 1979 Jun;291:531-44 PMID: 480247
  4. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
    Behav Neurosci. 1992 Apr;106(2):274-85 PMID: 1590953
  5. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells.
    Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8424-8 PMID: 8378314
  6. Cloning, expression and CNS distribution of Kv4.3, an A-type K+ channel alpha subunit.
    FEBS Lett. 1997 Jan 3;400(2):215-20 PMID: 9001401
  7. Selective damage to the hippocampal region blocks long-term retention of a natural and nonspatial stimulus-stimulus association.
    Hippocampus. 1995;5(6):546-56 PMID: 8646281
  8. The modulation of the rate of inactivation of the mKv1.1 K+ channel by the beta subunit, Kv beta 1 and lack of effect of a Kv beta 1 N-terminal peptide.
    FEBS Lett. 1996 Jan 15;378(3):250-2 PMID: 8557111
  9. Molecular cloning and functional expression of a novel potassium channel beta-subunit from human atrium.
    FEBS Lett. 1995 Mar 13;361(1):13-6 PMID: 7890032
  10. Mouse brain potassium channel beta1 subunit mRNA: cloning and distribution during development.
    J Neurobiol. 1998 Feb 5;34(2):135-50 PMID: 9468385
  11. Separable Kvbeta subunit domains alter expression and gating of potassium channels.
    J Biol Chem. 1997 Oct 10;272(41):25824-31 PMID: 9325312
  12. A potassium channel beta subunit related to the aldo-keto reductase superfamily is encoded by the Drosophila hyperkinetic locus.
    Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6763-7 PMID: 7542775
  13. Drosophila mutations that alter ionic conduction disrupt acquisition and retention of a conditioned odor avoidance response.
    J Neurogenet. 1986 Jul;3(4):187-201 PMID: 2427679
  14. Immunohistochemical localization of five members of the Kv1 channel subunits: contrasting subcellular locations and neuron-specific co-localizations in rat brain.
    Eur J Neurosci. 1995 Nov 1;7(11):2189-205 PMID: 8563969
  15. Heterogeneous Expression Patterns of Mammalian Potassium Channel Genes in Developing and Adult Rat Brain.
    Eur J Neurosci. 1992;4(12):1296-1308 PMID: 12106393
  16. Characterization of a voltage-gated K+ channel beta subunit expressed in human heart.
    Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6309-13 PMID: 7603988
  17. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice.
    Cell. 1991 Feb 22;64(4):693-702 PMID: 1997203
  18. Functional characterization of Kv channel beta-subunits from rat brain.
    J Physiol. 1996 Jun 15;493 ( Pt 3):625-33 PMID: 8799886
  19. The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.
    Cell. 1996 Dec 27;87(7):1327-38 PMID: 8980238
  20. Kinetic study and numerical reconstruction of A-type current in granule cells of rat cerebellar slices.
    J Neurophysiol. 1993 Jun;69(6):2222-31 PMID: 8394414
  21. In vivo functional role of the Drosophila hyperkinetic beta subunit in gating and inactivation of Shaker K+ channels.
    Biophys J. 1996 Dec;71(6):3167-76 PMID: 8968587
  22. Potassium currents in hippocampal pyramidal cells.
    Prog Brain Res. 1990;83:161-87 PMID: 2203097
  23. The alpha-Ca2+/calmodulin kinase II: a bidirectional modulator of presynaptic plasticity.
    Neuron. 1995 Mar;14(3):591-7 PMID: 7695905
  24. Place navigation impaired in rats with hippocampal lesions.
    Nature. 1982 Jun 24;297(5868):681-3 PMID: 7088155
  25. Acetylcholine and memory.
    Trends Neurosci. 1993 Jun;16(6):218-22 PMID: 7688162
  26. Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation.
    Trends Neurosci. 1996 Apr;19(4):150-4 PMID: 8658599
  27. A comparison of the contributions of the frontal and parietal association cortex to spatial localization in rats.
    Behav Neurosci. 1983 Feb;97(1):13-27 PMID: 6838719
  28. Calcium-dependent afterhyperpolarization and learning in young and aging hippocampus.
    Life Sci. 1996;59(5-6):413-20 PMID: 8761329
  29. A novel beta subunit increases rate of inactivation of specific voltage-gated potassium channel alpha subunits.
    J Biol Chem. 1995 Mar 17;270(11):6272-7 PMID: 7890764
  30. Serotonin modulates a specific potassium current in the sensory neurons that show presynaptic facilitation in Aplysia.
    Proc Natl Acad Sci U S A. 1982 Sep;79(18):5713-7 PMID: 6957886
  31. Presynaptic potassium channels.
    Curr Opin Neurobiol. 1996 Jun;6(3):338-41 PMID: 8794077
  32. A novel K+ channel beta-subunit (hKv beta 1.3) is produced via alternative mRNA splicing.
    J Biol Chem. 1995 Dec 1;270(48):28531-4 PMID: 7499366
  33. Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events.
    Science. 1986 May 23;232(4753):985-8 PMID: 3704635
  34. Swimming navigation and structural variations of the infrapyramidal mossy fibers in the hippocampus of the mouse.
    Hippocampus. 1991 Jul;1(3):315-28 PMID: 1669312
  35. Changes in membrane currents during Pavlovian conditioning of single cortical neurons.
    Brain Res. 1991 Jan 18;539(1):76-84 PMID: 2015505
  36. Cellular and molecular analysis of associative learning and memory in Hermissenda.
    Trends Neurosci. 1988 Apr;11(4):136-47 PMID: 2469181
  37. Subcellular segregation of two A-type K+ channel proteins in rat central neurons.
    Neuron. 1992 Aug;9(2):271-84 PMID: 1497894
  38. Kv beta 1 subunit binding specific for shaker-related potassium channel alpha subunits.
    Neuron. 1996 Feb;16(2):455-63 PMID: 8789960
  39. The role of K+ currents in frequency-dependent spike broadening in Aplysia R20 neurons: a dynamic-clamp analysis.
    J Neurosci. 1996 Jul 1;16(13):4089-101 PMID: 8753871
  40. Calcium-mediated reduction of ionic currents: a biophysical memory trace.
    Science. 1984 Nov 30;226(4678):1037-45 PMID: 6093258
  41. Transmission by presynaptic spike-like depolarization in the squid giant synapse.
    Proc Natl Acad Sci U S A. 1982 Apr;79(7):2415-9 PMID: 6954549
  42. Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals.
    Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):380-4 PMID: 1988937
  43. Voltage-gated K+ channel beta subunits: expression and distribution of Kv beta 1 and Kv beta 2 in adult rat brain.
    J Neurosci. 1996 Aug 15;16(16):4846-60 PMID: 8756417
  44. Spaced training induces normal long-term memory in CREB mutant mice.
    Curr Biol. 1997 Jan 1;7(1):1-11 PMID: 8999994
  45. Characterization of a mammalian cDNA for an inactivating voltage-sensitive K+ channel.
    Neuron. 1991 Sep;7(3):471-83 PMID: 1840649
  46. Storage of 7 +/- 2 short-term memories in oscillatory subcycles.
    Science. 1995 Mar 10;267(5203):1512-5 PMID: 7878473
  47. Differential expression of Shaw-related K+ channels in the rat central nervous system.
    J Neurosci. 1994 Mar;14(3 Pt 1):949-72 PMID: 8120636
  48. Diversity and ubiquity of K channels.
    Neuroscience. 1988 Jun;25(3):729-49 PMID: 2457185
  49. Selective interaction of voltage-gated K+ channel beta-subunits with alpha-subunits.
    J Biol Chem. 1996 Mar 22;271(12):7084-9 PMID: 8636142
  50. NAB domain is essential for the subunit assembly of both alpha-alpha and alpha-beta complexes of shaker-like potassium channels.
    Neuron. 1996 Feb;16(2):441-53 PMID: 8789959
  51. Alternative splicing of the human Shaker K+ channel beta 1 gene and functional expression of the beta 2 gene product.
    FEBS Lett. 1995 Aug 14;370(1-2):32-6 PMID: 7649300
  52. Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells.
    J Physiol. 1987 Apr;385:733-59 PMID: 2443676
  53. Dissociation of hippocampal and striatal contributions to spatial navigation in the water maze.
    Neurobiol Learn Mem. 1996 Nov;66(3):305-23 PMID: 8946424
  54. Serotonin receptors in cognitive behaviors.
    Curr Opin Neurobiol. 1997 Apr;7(2):243-54 PMID: 9142756
  55. K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons.
    Nature. 1997 Jun 26;387(6636):869-75 PMID: 9202119
  56. Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4430-4 PMID: 9114006
  57. Cloned potassium channels from eukaryotes and prokaryotes.
    Annu Rev Neurosci. 1997;20:91-123 PMID: 9056709
  58. Bursts as a unit of neural information: making unreliable synapses reliable.
    Trends Neurosci. 1997 Jan;20(1):38-43 PMID: 9004418
  59. A genetic test of the effects of mutations in PKA on mossy fiber LTP and its relation to spatial and contextual learning.
    Cell. 1995 Dec 29;83(7):1211-22 PMID: 8548807
  60. Modality-specific retrograde amnesia of fear.
    Science. 1992 May 1;256(5057):675-7 PMID: 1585183
  61. Action-potential propagation gated by an axonal I(A)-like K+ conductance in hippocampus.
    Nature. 1997 Sep 18;389(6648):286-9 PMID: 9305843
  62. Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.
    Nature. 1994 May 26;369(6478):289-94 PMID: 8183366
  63. Subtypes of K+ channels differentiated by the effect of K+ channel openers upon K+ channel blocker-induced seizures.
    Brain Res. 1989 Aug 21;495(1):189-92 PMID: 2550110
  64. Impaired motor learning performance in cerebellar En-2 mutant mice.
    Behav Neurosci. 1996 Feb;110(1):126-33 PMID: 8652061
  65. Structural and functional characterization of human potassium channel subunit beta 1 (KCNA1B).
    Neuropharmacology. 1996;35(7):787-95 PMID: 8938711
  66. Beta subunits promote K+ channel surface expression through effects early in biosynthesis.
    Neuron. 1996 Apr;16(4):843-52 PMID: 8608002
  67. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein.
    Cell. 1994 Oct 7;79(1):59-68 PMID: 7923378
  68. Differential spatiotemporal expression of K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro.
    J Neurosci. 1995 May;15(5 Pt 2):3840-51 PMID: 7751950
  69. Gene targeting and the biology of learning and memory.
    Annu Rev Genet. 1997;31:527-46 PMID: 9442906
  70. Neural and molecular bases of nonassociative and associative learning in Aplysia.
    Ann N Y Acad Sci. 1991;627:124-49 PMID: 1679307
  71. Calcium influx and transmitter release in a fast CNS synapse.
    Nature. 1996 Oct 3;383(6599):431-4 PMID: 8837774
  72. Phosphorylation of a K+ channel alpha subunit modulates the inactivation conferred by a beta subunit. Involvement of cytoskeleton.
    J Biol Chem. 1996 Nov 15;271(46):29321-8 PMID: 8910593
Article Info
Journal
Learning & memory (Cold Spring Harbor, N.Y.)
Abbr.
Learn Mem
ISSN
1072-0502
Published
1998-00-00
Pages
257-73
Language
English
Region
United States
NLM ID
9435678
PMCID
PMC311244
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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