TABLE 7

KV1.6 channels

Channel name KV1.61,2,3,4,5
Description Voltage-gated potassium channel, delayed rectifier
Other names HBK2, MK1.6, RCK2, KV2
Molecular information Human: 528aa, NM_002235, chr. 12p13.3,6 KCNA6, GeneID: 3742, PMID:23473051
Mouse: 529aa, NM_013568, chr. 6
Rat: 530 aa, XM_575671 (predicted), chr. 4q42
Associated subunits KVβ1, KVβ2,7,8 Caspr218
Functional assays Voltage-clamp
Current Delayed rectifier
Conductance 9pS1
Ion selectivity K+-selective
Activation Va = —20 mV; ka = 8 mV1
Inactivation Kh = —432; τh = > 3 s1
Activators None
Gating inhibitors None
Blockers α-Dendrotoxin (20 nM),1 10-N-methylcarbamoyl-3,7-bis(dimethylamino)phenothiazine (10 nM,1 200 nM3), 4-aminopyridine (1.5 mM),1,3 tetraethyammonium (7 mM),1,3 ShK (160 pM),9 HgTX (9.6 pM),10 BgK (W5Y/F6A/Y26F)11
Radioligands 125I-BgK (W5Y/F6A/Y26F),11125I-HgTX
Channel distribution Brain, colon, germ cell, heart, lung, ovary, testis, astrocytes, pulmonary artery smooth muscle cells, oligodendrocytes1,3,4,5,8,12,13,14,15,16
Physiological functions Regulator of membrane potential in neurons
Mutations and pathophysiology No K+ channel clustering in optic nerves of hypomyelinating Shiverer mice
Pharmacological significance Not established
Comments Can coassemble with other KV1 family members in heteromultimers but not with members of other KV families; intronless coding region; N terminus contains an N terminus inactivation prevention (NIP) domain;17 mammalian Shaker-related family

  • aa, amino acids; chr., chromosome; HgTx, hongotoxin.

  • ↵1. Grupe A, Schroter KH, Ruppersberg JP, Stocker M, Drewes T, Beckh S, and Pongs O (1990) Cloning and expression of a human voltage-gated potassium channel: a novel member of the RCK potassium channel family. EMBO J 9:1749-1756

  • ↵2. Guihard G, Bellocq C, Grelet E, and Escande D (2003) Human Kv1.6 current displays a C-type-like inactivation when re-expressed in cos-7 cells. Biochem Biophys Res Commun 311:83-89

  • ↵3. Swanson R, Marshall J, Smith JS, Williams JB, Boyle MB, Folander K, Luneau CJ, Antanavage J, Oliva C, Buhrow SA, et al. (1990) Cloning and expression of cDNA, and genomic clones encoding three delayed rectifier potassium channels in rat brain. Neuron 4:929-939

  • ↵4. Migeon MB, Street VA, Demas VP, and Tempel BL (1992) Cloning, sequence and chromosomal localization of MK6, a murine potassium channel gene. Epilepsy Res Suppl 9:173-180

  • ↵5. Ramashwami M, Gautam M, Kamb AA, Rudy B, Tanouye MA, and Mathew MK (1990) Human potassium channel genes: molecular cloning and functional expression. Mol Cell Neurosci 1:214-223

  • ↵6. Albrecht B, Weber K, and Pongs O (1995) Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13. Receptors Channels 3:213-220

  • ↵7. Rhodes KJ, Strassle BW, Monaghan MM, Bekele-Arcuri Z, Matos MF, and Trimmer JS (1997) Association and colocalization of the Kvβ1 and Kvβ2β-subunits with Kv1 α-subunits in mammalian brain K+ channel complexes. J Neurosci 17:8246-8258

  • ↵8. Rasband MN, Trimmer JS, Peles E, Levinson SR, and Shrager P (1999) K+ channel distribution and clustering in developing and hypomyelinated axons of the optic nerve. J Neurocytol 28:319-331

  • ↵9. Kalman K, Pennington MW, Lanigan MD, Nguyen A, Rauer H, Mahnir V, Paschetto K, Kern WR, Grissmer S, Gutman GA, et al. (1998) ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide. J Biol Chem 273:32697-32707

  • ↵10. Koschak A, Bugianesi RM, Mitterdorfer J, Kaczorowski GJ, Garcia ML, and Knaus HG (1998) Subunit composition of brain voltage-gated potassium channels determined by hongotoxin-1, a novel peptide derived from Centruroides limbatus venom. J Biol Chem 273:2639-2644

  • ↵11. Racape J, Lecoq A, Romi-Lebrun R, Liu J, Kohler M, Garcia ML, Menez A, and Gasparini S (2002) Characterization of a novel radio labeled peptide selective for a subpopulation of voltage-gated potassium channels in mammalian brain. J Biol Chem 277:3886-3893

  • ↵12. UniGene Cluster Hs0.301306

  • ↵13. Scott VE, Muniz ZM, Sewing S, Lichtinghagen R, Parcej DN, Pongs O, Dolly JO (1994) Antibodies specific for distinct Kv subunits unveil a heterooligomeric basis for subtypes of α-dendrotoxin-sensitive K+ channels in bovine brain. Biochemistry 33:1617-1623

  • ↵14. Smart SL, Bosma MM, and Tempel BL (1997) Identification of the delayed rectifier potassium channel, Kv1.6, in cultured astrocytes. Glia 20:127-134

  • ↵15. Yuan XJ, Wang J, Juhaszova M, Golovina VA, and Rubin LJ (1998) Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells. Am J Physiol 274:L621-L635

  • ↵16. Koh SD, Ward SM, Dick GM, Epperson A, Bonner HP, Sanders KM, Horowitz B, and Kenyon JL (1999) Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle. J Physiol 515:475-487

  • ↵17. Roeper J, Sewing S, Zhang Y, Sommer T, Wanner SG, and Pongs O (1998) NIP domain prevents N-type inactivation in voltage-gated potassium channels. Nature (Lond) 391:390-393

  • ↵18. Polliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer JL, Trimmer JS, Shrager P, and Peles E (1999) Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron 24:1037-1047