TABLE 6

KV1.5 channels

Channel name KV1.5
Description Voltage-gated potassium channel, delayed rectifier
Other names HpCN1, HK2, HCK1, KV1, fHK, RK3, RMK2, HuK (II)1,2,3,4,5,6,7,8
Molecular information Human: 613aa, NM_002234, chr. 12p13.3,8,9,10 KCNA5, GeneID: 3741, PMID: 19863823
Mouse: 602aa, NM_002234, chr. 6
Rat: 602aa, NM_012972, chr. 4q42-44
Associated subunits KVβ1, KVβ2, KCNA3B, Src tyrosine kinase, fyn, KChaP, α-actinin-2, caveolin, synapse-associated protein 97 (SAP97)11,12,13,14,15,16,17,18,19,20,21
Functional assays Voltage-clamp
Current Ultrarapid-activating K+ current in heart (IKur)22,23
Conductance 8pS24
Ion selectivity K+
Activation Voltage, Va = —14 mV; ka = 6—12 mV22,24
Inactivation Vh = —25 to —10 mV; kh = 3—5 mV; τh1 = 460 ms; τh2 = 5 s (40 mV)22,24
Activators None
Gating inhibitors None
Blockers S9947 (420 nM), 4-aminopyridine (270 μM), capsaicin (23 μM), resiniferatoxin (26 μM), flecainide (101 μM), nifedipine (81 μM), diltiazem (115 μM), tetraethyammonium (330 mM), clofilium inside (140 nM), bupivacaine (4.1 μM), propafenone (4.4 μM),24,25,26 quinidine (0.6 μM)27
Radioligands None
Channel distribution Aorta, colon, kidney, pooled colon, kidney, stomach, smooth muscle, whole embryo, hippocampus and cortex (oligodendrocytes, microglia, Schwann cells), pituitary, pulmonary artery1,2,3,4,5,6,7,28,29,30,31,32,33
Physiological functions KV1.5 has properties similar to the ultrarapidly activating IKur current in the heart, and antisense-targeting KV1.5 suppresses IKur currents almost 50%22,23; maintains membrane potential that modulates electrical excitability in neurons
Mutations and pathophysiology Not established
Pharmacological significance Potential use in management of atrial fibrillation via blockade of IKur34,35
Comments Can coassemble with other 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.

  • ↵1. 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

  • ↵2. 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

  • ↵3. Philipson LH, Hice RE, Schaefer K, LaMendola J, Bell GI, Nelson DJ, and Steiner DF (1991) Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Proc Natl Acad Sci USA 88:53-57

  • ↵4. 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

  • ↵5. 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

  • ↵6. Tamkun MM, Knoth KM, Walbridge JA, Kroemer H, Roden DM, and Glover DM (1991) Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB J 5:331-337

  • ↵7. 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

  • ↵8. Curran ME, Landes GM, and Keating MT (1992) Molecular cloning, characterization, and genomic localization of a human potassium channel gene. Genomics 12:729-737

  • ↵9. Phromchotikul T, Browne DL, Curran ME, Keating MT, and Litt M (1993) Dinucleotide repeat polymorphism at the KCNA5 locus. Hum Mol Genet 2:1512

  • ↵10. 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

  • ↵11. Sewing S, Roeper J, and Pongs O (1996) Kv β 1 subunit binding specific for shaker-related potassium channel α subunits. Neuron 16:455-463

  • ↵12. Uebele VN, England SK, Chaudhary A, Tamkun MM, and Snyders DJ (1996) Functional differences in Kv1.5 currents expressed in mammalian cell lines are due to the presence of endogenous Kv β 2.1 subunits. J Biol Chem 271:2406-2412

  • ↵13. 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

  • ↵14. 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

  • ↵15. Holmes TC, Fadool DA, Ren R, and Levitan IB (1996) Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain. Science (Wash DC) 274:2089-2091

  • ↵16. Sobko A, Peretz A, and Attali B (1998) Constitutive activation of delayed-rectifier potassium channels by a src family tyrosine kinase in Schwann cells. EMBO J 17:4723-4734

  • ↵17. Wible BA, Yang Q, Kuryshev YA, Accili EA, and Brown AM (1998) Cloning and expression of a novel K+ channel regulatory protein, KchAP. J Biol Chem 273:11745-11751

  • ↵18. Leicher T, Bahring R, Isbrandt D, and Pongs O (1998) Co expression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium channel. J Biol Chem 273:35095-35101

  • ↵19. Maruoka ND, Steele DF, Au BP, Dan P, Zhang X, Moore ED, and Fedida D (2000) α-Actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells. FEBS Lett 473:188-194

  • ↵20. Martens JR, Sakamoto N, Sullivan SA, Grobaski TD, and Tamkun MM (2001) Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations: targeting of Kv1.5 to caveolae. J Biol Chem 276:8409-8414

  • ↵21. Murata M, Buckett PD, Zhou J, Brunner M, Folco E, and Koren G (2001) SAP97 interacts with Kv1.5 in heterologous expression systems. Am J Physiol Heart Circ Physiol 281:H2575-H2584

  • ↵22. Snyders DJ, Tamkun MM, and Bennett PB (1993) A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression. J Gen Physiol 101:513-543

  • ↵23. Feng J, Wible B, Li GR, Wang Z, and Nattle S (1997) Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes. Circ Res. 80:572-579

  • ↵24. 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

  • ↵25. Malayev AA, Nelson DJ, and Philipson LH (1995) Mechanism of clofilium block of the human Kv1.5 delayed rectifier potassium channel. Mol Pharmacol 47:198-205

  • ↵26. Franqueza L, Longobardo M, Vicente J, Delpon E, Tamkun MM, Tamargo J, Snyders DJ, and Valenzuela C (1997) Molecular determinants of stereo selective bupivacaine block of hKv1.5 channels. Circ Res 81:1053-1064

  • ↵27. Snyders J, Knoth KM, Roberds SL, and Tamkun M.M (1992) Time-, voltage-, and state-dependent block by quinidine of a cloned human cardiac potassium channel. Mol Pharmacol 41:322-330

  • ↵28. UniGene Cluster Hs0.150208; OMIM no. 176267

  • ↵29. Kotecha SA and Schlichter LC (1999) A Kv1.5 to Kv1.3 switch in endogenous hippocampal microglia and a role in proliferation. J Neurosci 19:10680-10693

  • ↵30. Sobko A, Peretz A, Shirihai O, Etkin S, Cherepanova V, Dagan D, and Attali B (1998) Heteromultimeric delayed-rectifier K+ channels in Schwann cells: develo pMental expression and role in cell proliferation. J Neurosci 18:10398-10408

  • ↵31. Chittajallu R, Chen Y, Wang H, Yuan X, Ghiani CA, Heckman T, McBain CJ, and Gallo V (2002) Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle. Proc Natl Acad Sci USA 99:2350-2355

  • ↵32. Takimoto K, Fomina AF, Gealy R, Trimmer JS, and Levitan ES (1993) Dexamethasone rapidly induces Kv1.5 K+ channel gene transcription and expression in clonal pituitary cells. Neuron 11:359-369

  • ↵33. Wang J, Juhaszova M, Rubin LJ, and Yuan XJ (1997) Hypoxia inhibits gene expression of voltage-gated K+ channel α subunits in pulmonary artery smooth muscle cells. J Clin Invest 100:2347-2353

  • ↵34. Van Wagoner DR, Pond AL, McCarthy PM, Trimmer JS, and Nerbonne JM (1997) Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ Res 80:772-781

  • ↵35. Brundel BJ, Van Gelder IC, Henning RH, Tuinenburg AE, Wietses M, Grandjean JG, Wilde AA, Van Gilst WH, and Crijns HJ (2001) Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels. J Am Coll Cardiol 37:926-932