TABLE 2

KV1.1 channels

Channel name KV1.11,2,3,4,5,6
Description Voltage-gated potassium channel, delayed rectifier
Other names HuK (I), MBK1, MK1, RCK1, RBK1, HBK1
Molecular information Human: 494 aa, NM_000217, chr. 12p13.3,7,8 KCNA1, GeneID: 3736, PMID: 134929735
Mouse: 495aa, NM_010595, chr. 6
Rat: 495aa, NM_173095, chr. 4q42
Associated subunits KVβ1, KVβ2, PSD95, synapse-associated protein 97 (SAP97), SNAP251,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19
Functional assays Voltage-clamp
Current Voltage-gated potassium channel in neurons and skeletal muscle
Conductance 10pS20
Ion selectivity K+ (1) > Rb+ (0.8) > NH4+ (0.1)
Activation Va = -32 mV; ka = 8.5 mV; τn = 5 ms (-32 mV)20,21
Inactivation Vh = -51 mV; kh = 3 mV; τh = 11 s (40 mV)20,21
Activators None
Gating inhibitors None
Blockers Tetraethyammonium (0.3 mM), DTX (20 nM), DTX-K, ShK (16 pM), 10-N-methylcarbamoyl-3,7-bis(dimethylamino)phenothiazine (490 nM), 4-aminopyridine (290 μM), capsaicin (29 μM), resiniferatoxin (9 μM), flecainide (209 μM), nifedipine (96 μM), diltiazem (144 μM), kaliotoxin (41 nM), hongotoxin-1, margatoxin20,22,23,24
Radioligands 125I-DTX, 125I-BgK25,26
Channel distribution Brain, heart, retina, skeletal muscle, islets27,28,29,30,31
Physiological functions Maintaining membrane potential, modulating electrical excitability in neurons and muscle
Mutations and pathophysiology Episodic ataxia/myokymia syndrome type 18,32,33,34
Pharmacological significance Not established
Comments KV1.1 can coassemble with others in the KV1 family members in heteromultimers, but not with members of other KV families; intronless coding region; mammalian Shaker-related family

  • aa, amino acids; chr., chromosome; DTX, dendrotoxin; ShK, Stychodactyla helianthus toxin; BgK, Bundosoma granulifera toxin.

  • ↵1. Tempel BL, Jan YN, and Jan LY (1988) Cloning of a probable potassium channel gene from mouse brain. Nature (Lond) 332:837-839

  • ↵2. Baumann A, Grupe A, Ackermann A, and Pongs O (1988) Structure of the voltage-dependent potassium channel is highly conserved from Drosophila to vertebrate central nervous systems. EMBO J 7:2457-2463

  • ↵3. Kamb A, Weir M, Rudy B, Varmus H, and Kenyon C (1989) Identification of genes from pattern formation, tyrosine kinase, and potassium channel families by DNA amplification. Proc Natl Acad Sci USA 86:4372-4376

  • ↵4. McKinnon D (1989) Isolation of a cDNA clone coding for a putative second potassium channel indicates the existence of a gene family. J Biol Chem 264:8230-8236

  • ↵5. Christie MJ, Adelman JP, Douglass J, and North RA (1989) Expression of a cloned rat brain potassium channel in Xenopus oocytes. Science (Wash DC) 244:221-224

  • ↵6. Chandy KG, Williams CB, Spencer RH, Aguilar BA, Ghanshani S, Tempel BL, and Gutman GA (1990) A family of three mouse potassium channel genes with intronless coding regions. Science (Wash DC) 247:973-975

  • ↵7. Wymore RS, Korenberg JR, Kinoshita KD, Aiyar J, Coyne C, Chen XN, Hustad CM, Copeland NG, Gutman GA, Jenkins NA, et al. (1994) Genomic organization, nucleotide sequence, biophysical properties, and localization of the voltage-gated K+ channel gene KCNA4/Kv1.4 to mouse chromosome 2/human 11p14 and mapping of KCNC1/Kv3.1 to mouse 7/human 11p14.3-p15.2 and KCNA1/Kv1.1 to human 12p13. Genomics 20:191-202

  • ↵8. Browne DL, Gancher ST, Nutt JG, Brunt ER, Smith EA, Kramer P, and Litt, M (1994) Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet 8:136-140

  • ↵9. Curran ME, Landes GM, and Keating MT (992) Molecular cloning, characterization, and genomic localization of a human potassium channel gene. Genomics 12:729-737

  • ↵10. Scott VE, Rettig J, Parcej DN, Keen JN, Findlay JB, Pongs O, and Dolly JO (1994) Primary structure of a β subunit of α-dendrotoxin-sensitive K+ channels from bovine brain. Proc Natl Acad Sci USA 91:1637-1641

  • ↵11. Rettig J, Heinemann SH, Wunder F, Lorra C, Parcej DN, Dolly JO, and Pongs O (1994) Inactivation properties of voltage-gated K+ channels altered by presence of β-subunit. Nature (Lond) 369:289-294

  • ↵12. Wang Z, Kiehn J, Yang Q, Brown AM, and Wible BA (1996) Comparison of binding and block produced by alternatively spliced Kvβ1 subunits. J Biol Chem 271:28311-28317

  • ↵13. Stephens GJ, Cockett MI, Nawoschik SP, Schecter LE, and Owen DG (1996) The modulation of the rate of inactivation of the mKv1.1K+ channel by the β subunit, Kvβ1 and lack of effect of a Kvβ1 N-terminal peptide. FEBS Lett 378:250-252

  • ↵14. Heinemann SH, Rettig J, Graack HR, and Pongs O (1996) Functional characterization of Kv channel β-subunits from rat brain. J Physiol 493:625-633

  • ↵15. Jing J, Peretz T, Singer-Lahat D, Chikvashvili D, Thornhill WB, and Lotan, I (1997) Inactivation of a voltage-dependent K+ channel by β subunit Modulation by a phosphorylation-dependent inter-action between the distal C terminus of α subunit and cytoskeleton. J Biol Chem 272:14021-14024

  • ↵16. Rhodes KJ, Strassle BW, Monaghan MM, Bekele-Arcuri Z, Matos MF, and Trimmer JS (1997) Association and colocalization of the Kvβ1 and Kvβ2 β-subunits with Kv1 α-subunits in mammalian brain K+ channel complexes. J Neurosci 17:8246-8258

  • ↵17. Kim E. Niethammer M, Rothschild A, Jan YN, and Sheng M (1995) Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature (Lond) 378:85-88

  • ↵18. Doyle DA, Lee A, Lewis J, Kim E, Sheng M, and MacKinnon R (1996) Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell 85:1067-1076

  • ↵19. Tiffany AM, Manganas LN, Kim E, Hsueh YP, Sheng M, and Trimmer JS (2000) PSD-95 and SAP97 exhibit distinct mechanisms for regulating K+ channel surface expression and clustering. J Cell Biol 148:147-158

  • ↵20. Ji J, Tsuk S, Salapatek AM, Huang X, Chikvashvili D, Pasyk EA, Kang Y, Sheu L, Tsushima R, Diamant NE, et al. (2002) The 25-kDa synaptosome-associated protein (SNAP-25) binds and inhibits delayed rectifier potassium channels in secretory cells. J Biol Chem 277:20195-21204

  • ↵21. 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

  • ↵22. Stuhmer W. Ruppersberg JP, Schroter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, and Pongs O (1989) Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. EMBO J 8:3235-3244

  • ↵23. Robertson B, Owen D, Stow J, Butler C, and Newland C (1996) Novel effects of dendrotoxin homologues on subtypes of mammalian Kv1 potassium channels expressed in Xenopus oocytes. FEBS Lett 383:26-30

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

  • ↵25. Koch RO, Wanner SG, Koschak A, Hanner M, Schwarzer C, Kaczorowski GJ, Slaughter RS, Garcia ML, and Knaus HG (1997) Complex subunit assembly of neuronal voltage-gated K+ channels: basis for high-affinity toxin interactions and pharmacology. J Biol Chem 272:27577-27581

  • ↵26. Shamotienko O, Akhtar S, Sidera C, Meunier FA, Ink B, Weir M, and Dolly JO (1999) Recreation of neuronal Kv1 channel oligomers by expression in mammalian cells using Semliki Forest virus. Biochemistry 38:16766-16776

  • ↵27. 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

  • ↵28. Beckh S and Pongs O (1990) Members of the RCK potassium channel family are differentially expressed in the rat nervous system. EMBO J 9:777-782

  • ↵29. Tsaur ML, Sheng M, Lowenstein DH, Jan YN, and Jan LY (1992) Differential expression of K+ channel mRNAs in the rat brain and down-regulation in the hippocampus following seizures. Neuron 8:1055-1067

  • ↵30. Roberds SL and Tamkun MM (1991) Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart. Proc Natl Acad Sci USA 88:1798-1802

  • ↵31. Klumpp DJ, Farber DB, Bowes C, Song EJ, and Pinto LH (1991) The potassium channel MBK1 (Kv1.1) is expressed in the mouse retina. Cell Mol Neurobiol 11:611-622

  • ↵32. Matsubara H, Liman ER, Hess P, and Koren G (1991) Pretranslational mechanisms determine the type of potassium channels expressed in the rat skeletal and cardiac muscles. J Biol Chem 266:13324-13328

  • ↵33. Adelman JP, Bond CT, Pessia M, and Maylie J (1995) Episodic ataxia results from voltage-dependent potassium channels with altered functions. Neuron 15:1449-1454

  • ↵34. Zerr P, Adelman JP, and Maylie J (1998) Episodic n ataxia mutations in Kv1.1 alter potassium channel function by dominant negative effects or haplo insufficiency. J Neurosci 18:2842-2848

  • ↵35. Zerr P, Adelman JP, and Maylie J (1998) Characterization of three episodic ataxia mutations in the human Kv1.1 potassium channel. FEBS Lett 431:461-464