TABLE 3

KV1.2 channels

Channel name KV1.2
Description Voltage-gated potassium channel, delayed rectifier
Other names HuK (IV), MK2, BK2, RCK5, RAK, BGK5, XSha2, NGK1, HBK51,2,3,4,5,6,7,8
Molecular information Human: 499aa, NM_004974, chr. 1p13, KCNA2, GeneID: 3737, PMID: 225128333
Mouse: 499aa, NM_008417, chr. 3
Rat: 499aa, NM_012970 chr. 2q34
Associated subunits KVβ1, KVβ2, PSD95, synapse-associated protein 97 (SAP97), SNAP25, Caspr2, RhoA9,10,11,12,13,14,15,16,17
Functional assays Voltage-clamp
Current Delayed rectifier
Conductance 14–18pS18
Ion selectivity K+-selective
Activation Voltage-dependent, Va between 5 and 27 mV; ka = 13 mV; τn = 6 ms (60 mV)6,18
Inactivation Vh between -33 and -15 mV; kh ∼ 8 mV6,18
Activators None
Gating inhibitors None
Blockers 4-Aminopyridine (590 μM), capsaicin (45 μM), resiniferatoxin (31 μM), flecainide (217 μM), nifedipine (18 μM), diltiazem (187 μM), 10-N-methylcarbamoyl-3,7-bis(dimethylamino)phenothiazine (0.44 μM), DTX (17 nM), charybdotoxin (14 nM), margatoxin, natrexone (2 nM), tetraethyammonium (560 mM), H37 (18 μM), picrotoxin-Kα (32 pM), OsK2 (97 nM), BgK (25 nM), HgTx (pM), anandamide (2.7 μM)18,19,20,21,22,23
Radioligands 125I-DTX, 125I-HgTX1-A19Y/Y37F22
Channel distribution Brain (pons, medulla, cerebellum, inferior colliculus > hippocampus, thalamus, cerebral cortex, superior colliculus > midbrain, corpus striatum, olfactory bulb; neurons associated with mechanoreception and proprioception), spinal cord, Schwann cells, atrium, ventricle, islet, retina, smooth muscle, PC12 cells1,2,3,4,5,6,7,8,24,25,26,27,28,29,30
Physiological functions Maintaining membrane potential, modulating electrical excitability in neurons and muscle
Mutations and pathophysiology Not established
Pharmacological significance Not established
Comments Delayed rectifier potassium channel; can coassemble with other KV1 family members in heteromultimers but not with members of other KV families19,22,25,29,31; intronless coding region5; T1 domain in N terminus required for multimerization32; mammalian Shaker-related family

  • aa, amino acids; chr., chromosome; DTX, dendrotoxin; HgTX, hongotoxin.

  • ↵1. 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

  • ↵2. 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

  • ↵3. 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

  • ↵4. 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

  • ↵5. 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

  • ↵6. 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

  • ↵7. 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

  • ↵8. Paulmichl M, Nasmith P, Hellmiss R, Reed K, Boyle WA, Nerbonne JM, Peralta EG, and Clapham DE (1991) Cloning and expression of a rat cardiac delayed rectifier potassium channel. Proc Natl Acad Sci USA 88:7892-7895

  • ↵9. Grissmer S, Dethlefs B, Wasmuth JJ, Goldin AL, Gutman GA, Cahalan MD, and Chandy KG (1990) Expression and chromosomal localization of a lymphocyte K+ channel gene. Proc Natl Acad Sci USA 87:9411-9415

  • ↵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. 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

  • ↵13. Rhodes KJ, Keilbaugh SA, Barrezueta NX, Lopez KL, and Trimmer JS (1995) Association and colocalization of K+ channel α-and β-subunit polypeptides in rat brain. J Neurosci 15:5360-5371

  • ↵14. Shi G, Nakahira K, Hammond S, Rhodes KJ, Schechter LE, and Trimmer JS (1996) Beta subunits promote K+ channel surface expression through effects early in biosynthesis. Neuron 16:843-852

  • ↵15. 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

  • ↵16. Cachero TG, Morielli AD, and Peralta EG (1998) The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel. Cell 93:1077-1085

  • ↵17. Poliak 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

  • ↵18. 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

  • ↵19. 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

  • ↵20. 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

  • ↵21. Wulff H, Rauer H, During T, Hanselmann C, Ruff K, Wrisch A, Grissmer S, and Haensel W (1998) Alkoxypsoralens, novel nonpeptide blockers of Shaker-type K+ channels: synthesis and photoreactivity. J Med Chem 41:4542-4529

  • ↵22. Rogowski RS, Collins JH, O'Neill TJ, Gustafson TA, Werkman TR, Rogawski MA, Tenenholz TC, Weber DJ, and Blaustein MP (1996) Three new toxins from the scorpion Pandinus imperator selectively block certain voltage-gated K+ channels. Mol Pharmacol 50:1167-1177

  • ↵23. 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

  • ↵24. Poling JS, Rogawski MA, Salem NJ, and Vicini S (1996) Anandamide, an endogenous cannabinoid, inhibits Shaker-related voltage-gated K+ channels. Neuropharmacology 35:983-991

  • ↵25. UniGene Cluster Hs0.248139; Online Mendelian Inheritance in Man (OMIM) no. 176262

  • ↵26. Sheng M, Liao YJ, Jan YN, and Jan LY (1993) Presynaptic A-current based on heteromultimeric K+ channels detected in vivo. Nature (Lond) 365:72-75

  • ↵27. Sheng M, Tsaur ML, Jan YN, and Jan LY (1994) Contrasting subcellular localization of the Kv1.2 K+ channel subunit indifferent neurons of rat brain. J Neurosci 14:2408-2417

  • ↵28. Wang H, Kunkel DD, Schwartzkroin PA, and Tempel BL (1994) Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain. J Neurosci 14:4588-4599

  • ↵29. Klumpp DJ, Song EJ, Ito S, Sheng MH, Jan LY, and Pinto LH (1995) The Shaker-like potassium channels of the mouse rod bipolar cell and their contributions to the membrane current. J Neurosci 15:5004-5013

  • ↵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: developMental expression and role in cell proliferation. J Neurosci 18:10398-10408

  • ↵31. Coleman SK, Newcombe J, Pryke J, and Dolly JO (1999) Subunit composition of Kv1 channels in human CNS. J Neurochem 73:849-858

  • ↵32. Rasband MN, Park EW, Vanderah TW, Lai J, Porreca F, and Trimmer JS (2001) Distinct potassium channels on pain-sensing neurons. Proc Natl Acad Sci USA 98:13373-13378

  • ↵33. Minor DL, Lin YF, Mobley BC, Avelar A, Jan YN, Jan LY, and Berger JM (2000) The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel. Cell 102:657-670