TABLE 12

KV3.1 channels

Channel name KV3.1
Description Voltage-gated potassium channel, delayed rectifier
Other names Kv3.1,1 NGK2,2 KV4,3 KShIIIB,15 Raw2,4 type l channel in T cells5
Molecular information Human: 511aa, NM_004976, chr. 11p15,1,2,3,4,16 KCNC1, GeneID: 3746, PMID: 14004131
Mouse: 511aa, NM_008421, chr. 7
Rat: 585aa, NM_012856, chr. 1q22
Associated subunits Not established
Functional assays Electrophysiology
Current Delayed rectifier
Conductance 27pS1,5
Ion selectivity K+ (1) > Rb+ (0.76) > NH4+ (0.12) = Cs+ (0.12) > Na+ (0.004)6
Activation Va = 16 mV; ka = 10 mV; τa = 2 ms (40 mV)7
Inactivation τh = 630 ms (40 mV)1
Activators None
Gating inhibitors None
Blockers 4-Aminopyridine (29 μM), capsaicin (158 μM), resiniferatoxin (46 μM), flecainide (108 μM), nifedipine (131 μM), diltiazem (97 μM), cromakalim (237 μM), tetraethyammonium (0.2 mM)8
Radioligands None
Channel distribution Brain (cerebellum > globus pallidus, subthalamic nucleus, substantia nigra > reticular thalamic nuclei, cortical and hippocampal interneurons > inferior colliculi, cochlear and vestibular nuclei), skeletal muscle, human Louckes B cells, germ cell, lung, testis, AtT20 cell line9,10,11,12,13,19,20
Physiological functions Important for the high-firing frequency of auditory8 and fast-spiking GABAergic interneurons11,21; regulation of action potential duration in presynaptic terminals17,18
Mutations and pathophysiology Kv3.1-/- mice exhibit impaired motor skills and reduced muscle contraction force13; Kv3.1/Kv3.3 double knockout mice display severe ataxia, myoclonus, and hypersensitivity to ethanol14
Pharmacological significance Not established
Comments H-ras oncogene switches anterior pituitary-derived cells (AtT20) to a more neuron-like phenotype in parallel with the induction of expression of KV3.112; mammalian Shaw-related family
  • aa, amino acids; chr., chromosome.

  • 1. Grissmer S, Ghanshani S, Dethlefs B, McPherson JD, Wasmuth JJ, Gutman GA, Cahalan MD, and Chandy KG (1992) The Shaw-related potassium channel gene, Kv3.1, on human chromosome 11, encodes the type l K+ channel in T cells. J Biol Chem 267:20971-20979

  • 2. Yokoyama S, Imoto K, Kawamura T, Higashida H, Iwabe N, Miyata T, and Numa S (1989) Potassium channels from NG108–15 neuroblastoma-glioma hybrid cells: primary structure and functional expression from cDNAs. FEBS Lett 259:37-42

  • 3. Luneau CJ, Williams JB, Marshall J, Levitan ES, Oliva C, Smith JS, Antanavage J, Folander K, Stein RB, and Swanson R (1991) Alternative splicing contributes to K+ channel diversity in the mammalian central nervous system. Proc Natl Acad Sci USA 88:3932-3936

  • 4. Rettig J, Wunder F, Stocker M, Lichtinghagen R, Mastiaux F, Beckh S, Kues W, Pedarzani P, Schroter KH, Ruppersberg JP, et al. (1992) Characterization of a Shaw-related potassium channel family in rat brain. EMBO J 11:2473-2486

  • 5. Decoursey TE, Chandy KG, Gupta S, and Cahalan MD (1987) Two types of potassium channels in murine T lymphocytes. J Gen Physiol 89:379-404

  • 6. Shapiro MS and DeCoursey TE (1991) Selectivity and gating of the type l potassium channel in mouse lymphocytes. J Gen Physiol 97:1227-1250

  • 7. Shapiro MS and DeCoursey TE (1991) Permeant ion effects on gating kinetics of the type l potassium channel in mouse lymphocytes. J Gen Physiol 97:1251-1278

  • 8. Grissmer S, Nguyen AN, Aiyar J, Hanson DC, Mather RJ, Gutman GA, Karmilowicz MJ, Auperin DD, and Chandy KG (1994) Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol 45:1227-1234

  • 9. UniGene ClusterHs0.181768; OMIM no. 176258

  • 10. Wang LY, Gan L, Forsythe ID, and Kaczmarek LK (1998) Contribution of the Kv3.1 potassium channel to high-frequency firing in mouse auditory Neurones. J Physiol 509:183-194

  • 11. Massengill JL, Smith MA, Son DI, and O'Dowd DK (1997) Differential expression of K4-AP current sand Kv3.1 potassium channel transcripts in cortical neurons that develop distinct firing phenotypes. J Neurosci 17:3136-3147

  • 12. Hemmick LM, Perney TM, Flamm RE, Kaczmarek LK, and Birnberg NC (1992) Expression of the H-ras oncogene induces potassium conductance and neuron-specific potassium channel mRNAs in the AtT20 cell line. J Neurosci 12:2007-2014

  • 13. Ho CS, Grange RW, and Joho RH (1997) Pleiotropic effects of a disrupted K+ channel gene: reduced body weight, impaired motor skill and muscle contraction, but no seizures. Proc Natl Acad Sci USA 94:1533-1558

  • 14. Espinosa F, McMahon A, Chan E, Wang S, Ho CS, Heintz N, and Joho RH (2001) Alcohol hyper-sensitivity, increased locomotion, and spontaneous myoclonus in mice lacking the potassium channels Kv3.1 and Kv3.3. J Neurosci 21:6657-6665

  • 15. Haas M, Ward DC, Lee J, Roses AD, Clarke V, D'Eustachio P, Lau D, Vega-Saenz de Miera E, and Rudy B (1993) Localization of Shaw-related K+ channel genes on mouse and human chromosomes. Mamm Genome 4:711-715

  • 16. Ried T, Rudy B, Vega-Saenz de Miera E, Lau D, Ward DC, and Sen K (1993) Localization of a highly conserved potassium channel gene (NGK2-KV4; KCNC1) to chromosome 11p15. Genomics 15:405-411

  • 17. Ishikawa T, Nakamura Y, Saitoh N, Li WB, Iwasaki S, and Takahashi T (2003) Distinct roles of Kv1 and Kv3 potassium channels at the calyx of Held presynaptic terminal. J Neurosci 23:10445-10453

  • 18. Devaux J, Alcaraz G, Grinspan J, Bennett V, Joho R, Crest M, and Scherer SS (2003) Kv3.1b is a novel component of CNS nodes. J Neurosci 23:4509-4518

  • 19. Weiser M, Vega-Saenz de Miera E, Kentros C, Moreno H, Franzen L, Hillman D, Baker H, and Rudy B (1994) Differential expression of Shaw-related K+ channels in the rat central nervous system. J Neurosci 14:949-972

  • 20. Weiser M, Bueno E, Sekirnjak C, Martone ME, Baker H, Hillman D, Thornhill W, Ellisman M, and Rudy B (1995) The potassium channel subunit KV3.1b is localized to somatic and axonal membranes of specific populations of CNS neurons. J Neurosci 15,4298-4314

  • 21. Erisir A, Lau D, Rudy B, and Leonard CS (1999) The function of specific K+ channels in sustained high frequency firing of fast-spiking neocortical interneurons. J Neurophysiol 82:2476-2489