shaw potassium channels


Summary: A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.

Top Publications

  1. Minassian N, Lin M, Papazian D. Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13. J Physiol. 2012;590:1599-614 pubmed publisher
    ..Therefore, our data strongly suggest that changes in Kv3.3 gating contribute significantly to an early age of onset in SCA13...
  2. Hall M, Reutter W, Lindhorst T, Schwalbe R. Biochemical engineering of the N-acyl side chain of sialic acids alters the kinetics of a glycosylated potassium channel Kv3.1. FEBS Lett. 2011;585:3322-7 pubmed publisher
    ..Therefore, the N-acyl side chain of sialic acid is intimately connected with the activation and inactivation rates of this glycosylated potassium channel. ..
  3. Desai R, Kronengold J, Mei J, Forman S, Kaczmarek L. Protein kinase C modulates inactivation of Kv3.3 channels. J Biol Chem. 2008;283:22283-94 pubmed publisher
  4. Grissmer S, Ghanshani S, Dethlefs B, McPherson J, Wasmuth J, Gutman G, et al. The Shaw-related potassium channel gene, Kv3.1, on human chromosome 11, encodes the type l K+ channel in T cells. J Biol Chem. 1992;267:20971-9 pubmed
    ..1 encodes the voltage-gated type l K+ channel in lymphocytes. The Kv3.1 gene maps to human chromosome 11; the related Kv1.1 and Kv3.2 genes are localized on human chromosome 12, while the IsK gene maps to human chromosome 21. ..
  5. Ritter D, Ho C, O Leary M, Covarrubias M. Modulation of Kv3.4 channel N-type inactivation by protein kinase C shapes the action potential in dorsal root ganglion neurons. J Physiol. 2012;590:145-61 pubmed publisher
    ..We propose that the dramatic modulation of I(AHV) fast inactivation by PKC represents a novel mechanism of neural plasticity with potentially significant implications in the transition from acute to chronic pain. ..
  6. Hall M, Cartwright T, Fleming C, Schwalbe R. Importance of glycosylation on function of a potassium channel in neuroblastoma cells. PLoS ONE. 2011;6:e19317 pubmed publisher
    ..1 glycoprotein enhance outward ionic current kinetics, and neuronal migration. It is speculated that physiological changes which lead to a reduction in N-glycan attachment to proteins will alter the functions of the Kv3.1 channel. ..
  7. Mock A, RICHARDSON J, Hsieh J, Rinetti G, Papazian D. Functional effects of spinocerebellar ataxia type 13 mutations are conserved in zebrafish Kv3.3 channels. BMC Neurosci. 2010;11:99 pubmed publisher
    ..3 channels. The high degree of homology between human and zebrafish Kv3.3 channels suggests that the zebrafish will be a useful model system for studying pathogenic mechanisms in SCA13. ..
  8. Schwalbe R, Corey M, Cartwright T. Novel Kv3 glycoforms differentially expressed in adult mammalian brain contain sialylated N-glycans. Biochem Cell Biol. 2008;86:21-30 pubmed publisher
    ..We suggest that novel Kv3 glycoforms may endow differences in channel function and expression among regions throughout the central nervous system. ..
  9. Brooks N, Corey M, Schwalbe R. Characterization of N-glycosylation consensus sequences in the Kv3.1 channel. FEBS J. 2006;273:3287-300 pubmed
    ..1. We suggest that occupancy of the sites is critical for folding and maturation of the functional Kv3.1 at the cell surface. ..

More Information


  1. Waters M, Minassian N, Stevanin G, Figueroa K, Bannister J, Nolte D, et al. Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet. 2006;38:447-51 pubmed
    ..Our results establish a role for KCNC3 in phenotypes ranging from developmental disorders to adult-onset neurodegeneration and suggest voltage-gated K+ channels as candidates for additional neurodegenerative diseases. ..
  2. Klassen T, Buckingham S, Atherton D, Dacks J, Gallin W, Spencer A. Atypical phenotypes from flatworm Kv3 channels. J Neurophysiol. 2006;95:3035-46 pubmed
    ..These results demonstrate that broad phylogenetic sampling of proteins of a single family will reveal unexpected properties that lead to new interpretations of structure-function relationships. ..
  3. Shevchenko T, Teruyama R, Armstrong W. High-threshold, Kv3-like potassium currents in magnocellular neurosecretory neurons and their role in spike repolarization. J Neurophysiol. 2004;92:3043-55 pubmed
  4. Ozaita A, Martone M, Ellisman M, Rudy B. Differential subcellular localization of the two alternatively spliced isoforms of the Kv3.1 potassium channel subunit in brain. J Neurophysiol. 2002;88:394-408 pubmed
    ..1a protein in dendritic and somatic membrane, respectively. The results support the hypothesis that the alternative spliced C-termini of Kv3 subunits regulate their subcellular targeting in neurons...
  5. Antz C, Bauer T, Kalbacher H, Frank R, Covarrubias M, Kalbitzer H, et al. Control of K+ channel gating by protein phosphorylation: structural switches of the inactivation gate. Nat Struct Biol. 1999;6:146-50 pubmed
    ..These structural changes correlate with the distinct changes in binding and unbinding kinetics underlying the reduced inactivation potency of phosphorylated IDs. ..
  6. Tansey E, Chow A, Rudy B, McBain C. Developmental expression of potassium-channel subunit Kv3.2 within subpopulations of mouse hippocampal inhibitory interneurons. Hippocampus. 2002;12:137-48 pubmed
    ..The vast majority of these interneuron subpopulations possess a "fast-spiking" phenotype, consistent with a role for currents through Kv3.2 containing channels in determining action potential kinetics in these cells. ..
  7. Macica C, von Hehn C, Wang L, Ho C, Yokoyama S, Joho R, et al. Modulation of the kv3.1b potassium channel isoform adjusts the fidelity of the firing pattern of auditory neurons. J Neurosci. 2003;23:1133-41 pubmed
    ..Our results suggest that modulation of Kv3.1 by phosphorylation allows auditory neurons to tune their responses to different patterns of sensory stimulation. ..
  8. Waters M, Pulst S. Sca13. Cerebellum. 2008;7:165-9 pubmed publisher
    ..These mutations are expected to change the output characteristics of fast-spiking cerebellar neurons, where KCNC channels confer capacity for high-frequency repetitive firing. ..
  9. Elezgarai I, Diez J, Puente N, Azkue J, Benitez R, Bilbao A, et al. Subcellular localization of the voltage-dependent potassium channel Kv3.1b in postnatal and adult rat medial nucleus of the trapezoid body. Neuroscience. 2003;118:889-98 pubmed
    ..The presence of the channel in this system is crucial for the high-frequency synaptic transmission of auditory signals. ..
  10. Alonso Espinaco V, Elezgarai I, Díez García J, Puente N, Knopfel T, Grandes P. Subcellular localization of the voltage-gated potassium channels Kv3.1b and Kv3.3 in the cerebellar dentate nucleus of glutamic acid decarboxylase 67-green fluorescent protein transgenic mice. Neuroscience. 2008;155:1059-69 pubmed publisher
    ..3 potassium subunits are expressed in both GAD- and GAD+ cells, albeit at different densities and distribution. They likely contribute to the distinct biophysical properties of both GAD- and GAD+ neurons in the dentate nucleus. ..
  11. Friederich P, Dilger J, Isbrandt D, Sauter K, Pongs O, Urban B. Biophysical properties of Kv3.1 channels in SH-SY5Y human neuroblastoma cells. Receptors Channels. 2003;9:387-96 pubmed
    ..RT-PCR experiments amplified a cDNA fragment specific for human Kv3.1 channels. Activation gating parameters in outside-out patches were shifted by approximately 14 mV in the hyperpolarizing direction. ..
  12. Issa F, Mazzochi C, Mock A, Papazian D. Spinocerebellar ataxia type 13 mutant potassium channel alters neuronal excitability and causes locomotor deficits in zebrafish. J Neurosci. 2011;31:6831-41 pubmed publisher
  13. Cartwright T, Schwalbe R. Atypical sialylated N-glycan structures are attached to neuronal voltage-gated potassium channels. Biosci Rep. 2009;29:301-13 pubmed publisher
  14. Pacheco Otalora L, Skinner F, Oliveira M, Farrell B, Arshadmansab M, Pandari T, et al. Chronic deficit in the expression of voltage-gated potassium channel Kv3.4 subunit in the hippocampus of pilocarpine-treated epileptic rats. Brain Res. 2011;1368:308-16 pubmed publisher
    ..Down-regulation of Kv3.4 in mossy fibers may contribute to enhanced presynaptic excitability leading to recurrent seizures in the pilocarpine model of temporal lobe epilepsy. ..
  15. Figueroa K, Waters M, Garibyan V, Bird T, Gomez C, Ranum L, et al. Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13 (SCA13). PLoS ONE. 2011;6:e17811 pubmed publisher
    ..Our objective was to describe the frequency of mutations associated with KCNC3 in a large cohort of index patients with sporadic or familial ataxia presenting to three US ataxia clinics at academic medical centers...
  16. Wang Z, Robertson B, Fedida D. Gating currents from a Kv3 subfamily potassium channel: charge movement and modification by BDS-II toxin. J Physiol. 2007;584:755-67 pubmed
    ..However, the Q-V relationship remained well fitted by a single Boltzmann function. These data provide the first description of Kv3 gating currents and give further insight into the interaction of BDS toxins and Kv3 channels. ..
  17. Figueroa K, Minassian N, Stevanin G, Waters M, Garibyan V, Forlani S, et al. KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial ataxia patients. Hum Mutat. 2010;31:191-6 pubmed publisher
    ..Despite a phenotype reminiscent of the p.Phe448Leu mutation, segregating in a large early-onset French pedigree, the p.Arg423His mutation resulted in a nonfunctional subunit with a strong dominant-negative effect. ..
  18. Henderson Z, Lu C, Janzso G, Matto N, McKinley C, Yanagawa Y, et al. Distribution and role of Kv3.1b in neurons in the medial septum diagonal band complex. Neuroscience. 2010;166:952-69 pubmed publisher
    ..1 in the GABAergic neurons does not contribute to theta activity through fast spiking properties, but possibly by the regulation of transmitter release from axonal terminals. ..
  19. Goldman Wohl D, Chan E, Baird D, Heintz N. Kv3.3b: a novel Shaw type potassium channel expressed in terminally differentiated cerebellar Purkinje cells and deep cerebellar nuclei. J Neurosci. 1994;14:511-22 pubmed
    ..3b K+ channel function is restricted to terminally differentiated Purkinje cells, and that analysis of the mechanisms governing its expression in vivo and in vitro can reveal molecular mechanisms governing Purkinje cell differentiation. ..
  20. Lien C, Jonas P. Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons. J Neurosci. 2003;23:2058-68 pubmed
    ..In conclusion, Kv3 channels are necessary for the FS phenotype of OA interneurons, and several of their gating properties appear to be optimized for high-frequency repetitive activity. ..
  21. Deuchars S, Brooke R, Frater B, Deuchars J. Properties of interneurones in the intermediolateral cell column of the rat spinal cord: role of the potassium channel subunit Kv3.1. Neuroscience. 2001;106:433-46 pubmed
    ..These studies provide electrophysiological and morphological data on interneurones in the IML and indicate that the channels containing the Kv3.1 subunit are important in setting the firing pattern of these neurones. ..
  22. Chang S, Zagha E, Kwon E, Ozaita A, Bobik M, Martone M, et al. Distribution of Kv3.3 potassium channel subunits in distinct neuronal populations of mouse brain. J Comp Neurol. 2007;502:953-72 pubmed
    ..In this study, we identified additional populations and subcellular compartments that are likely to sustain high-frequency firing because of the expression of Kv3.3 and other Kv3 subunits. ..
  23. Abbott G, Butler M, Bendahhou S, Dalakas M, Ptacek L, Goldstein S. MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. Cell. 2001;104:217-31 pubmed
    ..Mutant MiRP2-Kv3.4 complexes exhibit reduced current density and diminished capacity to set RMP. Thus, MiRP2 operates with a classical potassium channel subunit to govern skeletal muscle function and pathophysiology...
  24. Burk K, Strzelczyk A, Reif P, Figueroa K, Pulst S, Zühlke C, et al. Mesial temporal lobe epilepsy in a patient with spinocerebellar ataxia type 13 (SCA13). Int J Neurosci. 2013;123:278-82 pubmed publisher
    ..This demonstrates that epilepsy of structural-metabolic cause may be contingent upon genetically defined channelopathies...
  25. Hodge J, Choi J, O Kane C, Griffith L. Shaw potassium channel genes in Drosophila. J Neurobiol. 2005;63:235-54 pubmed
    ..Whole cell recordings from ventral ganglion motor neurons expressing the truncated Shaw protein suggest that a major role of Shaw channels in these cells is to contribute to the resting potential. ..
  26. Rudy B, McBain C. Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing. Trends Neurosci. 2001;24:517-26 pubmed
  27. Deng Q, Rashid A, Fernandez F, Turner R, Maler L, Dunn R. A C-terminal domain directs Kv3.3 channels to dendrites. J Neurosci. 2005;25:11531-41 pubmed
    ..3 channels to the dendritic compartment. ..
  28. Brooke R, Atkinson L, Edwards I, Parson S, Deuchars J. Immunohistochemical localisation of the voltage gated potassium ion channel subunit Kv3.3 in the rat medulla oblongata and thoracic spinal cord. Brain Res. 2006;1070:101-15 pubmed
    ..This study provides evidence supporting a role for Kv3.3 subunits in regulating neuronal excitability and in the modulation of excitatory and inhibitory synaptic transmission in the medulla oblongata and spinal cord. ..
  29. Brooke R, Moores T, Morris N, Parson S, Deuchars J. Kv3 voltage-gated potassium channels regulate neurotransmitter release from mouse motor nerve terminals. Eur J Neurosci. 2004;20:3313-21 pubmed
    ..05-1 microM. The combined presynaptic localization of Kv3 subunits and pharmacological enhancement of EPP amplitude indicate that Kv3 channels regulate neurotransmitter release from presynaptic terminals at the NMJ. ..
  30. Rudy B, Chow A, Lau D, Amarillo Y, Ozaita A, Saganich M, et al. Contributions of Kv3 channels to neuronal excitability. Ann N Y Acad Sci. 1999;868:304-43 pubmed
    ..Experimental evidence has now become available showing that Kv3.1-Kv3.2 channels play critical roles in the generation of fast-spiking properties in cortical GABAergic interneurons. ..
  31. Dallas M, Atkinson L, Milligan C, Morris N, Lewis D, Deuchars S, et al. Localization and function of the Kv3.1b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii. J Physiol. 2005;562:655-72 pubmed
    ..Synaptic inputs evoked by stimulation of a region lacking Kv3.1b-IR neurones were not affected, correlating the presence of Kv3.1b in the TS with the pharmacological effects. ..
  32. Itri J, Michel S, Vansteensel M, Meijer J, Colwell C. Fast delayed rectifier potassium current is required for circadian neural activity. Nat Neurosci. 2005;8:650-6 pubmed
    ..We conclude that the FDR is necessary for the circadian modulation of electrical activity in SCN neurons and represents an important part of the ionic basis for the generation of rhythmic output. ..
  33. Rae J, Shepard A. Kv3.3 potassium channels in lens epithelium and corneal endothelium. Exp Eye Res. 2000;70:339-48 pubmed publisher
    ..3 channel produces an A-current although expression of constructs which lack the 5' region of the first start codon inactivate much more slowly than full-length constructs. This short hKv3.3 construct also shows changes in activation...
  34. Devaux J, Alcaraz G, Grinspan J, Bennett V, Joho R, Crest M, et al. Kv3.1b is a novel component of CNS nodes. J Neurosci. 2003;23:4509-18 pubmed
    ..These effects were also observed in Kv3.1-deficient mice. In conclusion, Kv3.1b is the first K+ channel subunit to be identified in CNS nodes; but Kv3.1b does not account for the effects of 4-aminopyridine on central myelinated tracts. ..
  35. Rettig J, Wunder F, Stocker M, Lichtinghagen R, Mastiaux F, Beckh S, et al. Characterization of a Shaw-related potassium channel family in rat brain. EMBO J. 1992;11:2473-86 pubmed
    ..A single neuron is able to express multiple, independently assembled potassium channels. ..
  36. Klemic K, Kirsch G, Jones S. U-type inactivation of Kv3.1 and Shaker potassium channels. Biophys J. 2001;81:814-26 pubmed
    ..We introduce the term U-type inactivation for the mechanism that is dominant in Kv2.1 and Kv3.1. U-type inactivation also makes a major but previously unrecognized contribution to slow inactivation of Shaker. ..
  37. Tiwari Woodruff S, Beltran Parrazal L, Charles A, Keck T, Vu T, Bronstein J. K+ channel KV3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development. Am J Physiol Cell Physiol. 2006;291:C687-98 pubmed
    ..1 K(+) current accounts for a significant component of the total K(+) current in cells of the Olg lineage and, in association with OSP/claudin-11, plays a significant role in OPC proliferation and migration and myelination of axons. ..
  38. Steinert J, Kopp Scheinpflug C, Baker C, Challiss R, Mistry R, Haustein M, et al. Nitric oxide is a volume transmitter regulating postsynaptic excitability at a glutamatergic synapse. Neuron. 2008;60:642-56 pubmed publisher
  39. Joho R, Hurlock E. The role of Kv3-type potassium channels in cerebellar physiology and behavior. Cerebellum. 2009;8:323-33 pubmed publisher
  40. Steinert J, Robinson S, Tong H, Haustein M, Kopp Scheinpflug C, Forsythe I. Nitric oxide is an activity-dependent regulator of target neuron intrinsic excitability. Neuron. 2011;71:291-305 pubmed publisher
    ..We conclude that nitric oxide is a homeostatic regulator, tuning neuronal excitability to the recent history of excitatory synaptic inputs over intervals of minutes to hours...
  41. Leicher T, Bähring R, Isbrandt D, Pongs O. Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium channel. J Biol Chem. 1998;273:35095-101 pubmed
    ..Thus, the expression of Kvbeta3.1 subunits potentially extends the possibilities to express diverse A-type Kv channels in the human brain. ..
  42. Shi H, Wang H, Han H, Xu D, Yang B, Nattel S, et al. Ultrarapid delayed rectifier K(+) current in H9c2 rat ventricular cell line: biophysical property and molecular identity. Cell Physiol Biochem. 2002;12:215-26 pubmed
    ..We conclude that the H9c2 cells at the myoblast stage express mainly I(Kur) and Kv3.1b may be a molecular component of the H9c2 I(Kur), and H9c2 cells provide a suitable system for studying I(Kur). ..
  43. Joho R, Marks G, Espinosa F. Kv3 potassium channels control the duration of different arousal states by distinct stochastic and clock-like mechanisms. Eur J Neurosci. 2006;23:1567-74 pubmed
    ..In contrast to the stochastic control of episode durations of wakefulness and SWS, the durations of both REMS states are normally distributed, indicating that the underlying control processes are fundamentally different. ..
  44. Zemel B, Muqeem T, Brown E, Goulão M, Urban M, Tymanskyj S, et al. Calcineurin Dysregulation Underlies Spinal Cord Injury-Induced K+ Channel Dysfunction in DRG Neurons. J Neurosci. 2017;37:8256-8272 pubmed publisher
    ..The results strongly suggest that CaN inhibition underlies SCI-induced dysfunction of Kv3.4 and the associated excitability changes through upregulation of the native regulator of CaN 1 (RCAN1). ..
  45. Zagha E, Manita S, Ross W, Rudy B. Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes. J Neurophysiol. 2010;103:3516-25 pubmed publisher
    ..These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease...
  46. Ahn H, Choi J, Choi B, Kim M, Rhie D, Yoon S, et al. Inhibition of the cloned delayed rectifier K+ channels, Kv1.5 and Kv3.1, by riluzole. Neuroscience. 2005;133:1007-19 pubmed
    ..Thus, riluzole inhibits both Kv1.5 and Kv3.1 currents in a concentration-dependent manner and interacts directly with Kv1.5 by preferentially binding to the inactivated and to the closed states of the channel. ..
  47. McDonald A, Mascagni F. Differential expression of Kv3.1b and Kv3.2 potassium channel subunits in interneurons of the basolateral amygdala. Neuroscience. 2006;138:537-47 pubmed
    ..1b subunit. The significance of Kv3.2 expression in some parvalbumin+ and somatostatin+ interneurons remains to be determined. ..
  48. Díez García J, Akemann W, Knopfel T. In vivo calcium imaging from genetically specified target cells in mouse cerebellum. Neuroimage. 2007;34:859-69 pubmed
    ..We expect that genetically targeted fluorescent calcium indicator proteins along with optical imaging techniques will be instrumental for the construction of macroscopic and microscopic maps of the function of specific brain circuits. ..
  49. Espinosa F, McMahon A, Chan E, Wang S, Ho C, Heintz N, et al. Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus in mice lacking the potassium channels Kv3.1 and Kv3.3. J Neurosci. 2001;21:6657-65 pubmed
    ..1 and Kv3.3 K(+) channels are unrelated and may be caused by localized dysfunction in different brain regions. ..
  50. Yeung S, Thompson D, Wang Z, Fedida D, Robertson B. Modulation of Kv3 subfamily potassium currents by the sea anemone toxin BDS: significance for CNS and biophysical studies. J Neurosci. 2005;25:8735-45 pubmed
    ..Our data will be informative for experiments designed to dissect out the roles of Kv3 subunits in CNS function and dysfunction. ..
  51. Hurlock E, McMahon A, Joho R. Purkinje-cell-restricted restoration of Kv3.3 function restores complex spikes and rescues motor coordination in Kcnc3 mutants. J Neurosci. 2008;28:4640-8 pubmed publisher
    ..Therefore, spike parameters requiring Kv3.3 function in Purkinje cells are involved in the ataxic null phenotype and motor coordination, but not motor learning. ..
  52. Soares D, Goldrick I, Lemon R, Kraskov A, Greensmith L, Kalmar B. Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque. J Comp Neurol. 2017;525:2164-2174 pubmed publisher
    ..Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. ..
  53. Hartig W, Singer A, Grosche J, Brauer K, Ottersen O, Bruckner G. Perineuronal nets in the rat medial nucleus of the trapezoid body surround neurons immunoreactive for various amino acids, calcium-binding proteins and the potassium channel subunit Kv3.1b. Brain Res. 2001;899:123-33 pubmed
    ..1b - as an established marker of fast-firing parvalbumin-containing neurons - supports the assumed function of PNs as a cation exchanger ensuring rapid ion transport as required by highly active nerve cells. ..