TABLE 10

KV2.1 channels

Channel name Kv2.11,2,3
Description Voltage-gated potassium channel, delayed rectifier
Other names hDRK1, DRK1
Molecular information Human: 858aa, NM_004975, chr. 20q13.2,4,5 KCNB1, GeneID: 3745, PMID: 808172335
Mouse: 857aa, NM_008420, chr. 2
Rat: 853aa, NM_013186, chr. 3q42
Associated subunits Kv5.1, Kv6.1—Kv6.3, Kv8.1, Kv9.1—Kv9.3, KChaP (binds to N terminus of Kv2.1), Fyn SH2 domain6,7,8,9,10,11,12,13,14,15
Functional assays Voltage-clamp
Current Kv2.1/Kv9.3 (delayed rectifier in oxygen-sensitive pulmonary artery),9 delayed rectifier current in hippocampal and globus pallidus neurons16,17
Conductance 8pS; on removal of K+, Kv2.1 displays a large Na+ conductance that is inhibited by low concentrations of K+2,18
Ion selectivity K+ > Rb+
Activation Voltage, Va = 12 mV; ka = 3 mV3
Inactivation Noninactivating
Activators Linoleic acid19
Gating inhibitors Hanatoxin (42 nM)20,21
Blockers Internal tetraethylammonium and tetrapentylammonium, internal Ba2+ (13 μM), external Ba2+ (30 mM), internal Mg2+, 4-AP (18 mM), halothane22,22,22,25
Radioligands None
Channel distribution Brain (cerebral cortex > hippocampus > cerebellum > olfactory bulb; restricted to neurons, where staining is present on dendrites and cell bodies but not on axons; Schwann cells), atria, ventricle, skeletal muscle, retina, cochlea, eye, germ cell, lung, PC12 cells, pulmonary arteries, insulinomas1,3,9,14,16,17,26,27,28,29,30,31,32,33
Physiological functions Maintaining membrane potential and modulating electrical excitability in neurons and muscle9,16,17
Mutations and pathophysiology Kv2.1 expression is reduced in chronic hypoxic pulmonary hypertension.30,32
Pharmacological significance Not established
Comments Ser857Asn polymorphism in 0—3% in different ethnic populations5; two other single nucleotide polymorphisms have been identified34; the 4-AP binding site is in the S6 inner vestibule.23 Mammalian Shab-related family.

  • aa, amino acids; chr., chromosome; 4-AP, 4-aminopyridine.

  • ↵1. Frech GC, Van Dongen AM, Schuster G, Brown AM, and Joho RH (1989) A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning. Nature (Lond) 340:642-645

  • ↵2. Hartmann HA, Kirsch GE, Drewe JA, Taglialatela M, Joho RH, and Brown AM (1991) Exchange of conduction pathways between two related K+ channels. Science (Wash DC) 251:942-944

  • ↵3. Albrecht B, Lorra C, Stocker M, and Pongs O (1993) Cloning and characterization of a human delayed rectifier potassium channel gene. Receptors Channels 1:99-110

  • ↵4. Melis R, Stauffer D, Zhao X, Zhu XL, Albrecht B, Pongs O, Brothman A, and Leppert M (1995) Physical and genetic localization of a Shab subfamily potassium channel (KCNB1) gene to chromosomal region 20q13.2. Genomics 25:285-287

  • ↵5. Mazzanti CM, Bergen A, Enoch MA, Michelini S, and Goldman D (1996) Identification of a Ser857-Asn857 substitution in DRK1 (KCNB1), population frequencies and lack of association to the low voltage α EEG trait. Hum Genet 98:134-137

  • ↵6. Post MA, Kirsch GE, and Brown AM (1996) Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and express a novel current. FEBS Lett 399:177-182

  • ↵7. Salinas M, de Weille J, Guillemare E, Lazdunski M, and Hugnot JP (1997) Modes of regulation of Shab K+ channel activity by the Kv8.1 subunit. J Biol Chem 272:8774-8780

  • ↵8. Salinas M, Duprat F, Heurteaux C, Hugnot JP, and Lazdunsk, M (1997) New modulatory α subunits for mammalian Shab K+ channels. J Biol Chem 272:24371-24379

  • ↵9. Patel AJ, Lazdunski M, and Honore E (1997) Kv2.1/Kv9.3, a novel ATP-dependent delayed-rectifier K+ channel in oxygen-sensitive pulmonary artery myocytes. EMBO J 16:6615-6625

  • ↵10. 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

  • ↵11. 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

  • ↵12. Kramer JW, Post MA, Brown AM, and Kirsch GE (1998) Modulation of potassium channel gating by co expression of Kv2.1 with regulatory Kv5.1 or Kv6.1 α-subunits. Am J Physiol 274:C1501-C1510

  • ↵13. Chiara MD, Monje F, Castellano A, and Lopez-Barneo J (1999) A small domain in the N terminus of the regulatory α-subunit Kv23 modulates Kv2.1 potassium channel gating. J Neurosci 19:6865-6873

  • ↵14. Kuryshev YA, Wible BA, Gudz TI, Ramirez AN, and Brown AM (2001) KChAP/Kvβ1.2 interactions and their effects on cardiac Kv channel expression. Am J Physiol Cell Physiol 281:C290-C299

  • ↵15. Sano Y, Mochizuki S, Miyake A, Kitada C, Inamura K, Yokoi H, Nozawa K, Matsushime H, and Furuichi, K (2002) Molecular cloning and characterization of Kv6.3, a novel modulatory subunit for voltage-gated K+ channel Kv2.1. FEBS Lett 512:230-234

  • ↵16. Murakoshi H, and Trimmer JS (1999) Identification of the Kv2.1 K+ channel as a major component of the delayed rectifier K+ current in rat hippocampal neurons. J Neurosci 19:1728-1735

  • ↵17. Baranauskas G, Tkatch T, and Surmeier DJ (1999) Delayed rectifier currents in rat globus pallidus neurons are attributable to Kv2.1 and Kv3.1/3.2 K+ channels. J Neurosci 19:6394-6404

  • ↵18. Korn SJ and Ikeda SR (1995) Permeation selectivity by competition in a delayed rectifier potassium channel. Science (Wash DC) 269:410-412

  • ↵19. McKay MC and Worley JF 3rd (2001) Linoleic acid both enhances activation and blocks Kv1.5 and Kv2.1 channels by two separate mechanisms. Am J Physiol Cell Physiol 281:C1277-C1284

  • ↵20. Swartz KJ and MacKinnon R (1995) An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula. Neuron 15:941-949

  • ↵21. Swartz KJ and MacKinnon R (1997) Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites. Neuron 18:665-673

  • ↵22. Taglialatela M, Vandongen AM, Drewe JA, Joho RH, Brown AM, and Kirsch GE (1991) Patterns of internal and external tetraethylammonium block in four homologous K+ channels. Mol Pharmacol 40:299-307

  • ↵23. Kirsch GE, Shieh CC, Drewe JA, Vener DF, and Brown AM (1993) Segmental exchanges define 4-aminopyridine binding and the inner mouth of K+ pores. Neuron 11:503-512

  • ↵24. Taglialatela M, Drewe JA, and Brown AM (1993) Barium blockade of a clonal potassium channel and its regulation by a critical pore residue. Mol Pharmacol 44:180-190

  • ↵25. Kulkarni RS, Zorn LJ, Anantharam V, Bayley H, and Treistman SN (1996) Inhibitory effects of ketamine and halothane on recombinant potassium channels from mammalian brain. Anesthesiology 84:900-909

  • ↵26. Trimmer JS (1991) Immunological identification and characterization of a delayed rectifier K+ channel polypeptide in rat brain. Proc Natl Acad Sci USA 88:10764-10768

  • ↵27. Hwang PM, Fotuhi M, Bredt DS, Cunningham AM, and Snyder SH (1993) Contrasting immunohistochemical localizations in rat brain of two novel K+ channels of the Shab subfamily. J Neurosci 13:1569-1576

  • ↵28. Sharma N, D'Arcangelo G, Kleinlaus A, Halegoua S, and Trimmer JS (1993) Nerve growth factor regulates the abundance and distribution of K+ channels in PC12 cells. J Cell Biol 123:1835-1843

  • ↵29. Scannevin RH, Murakoshi H, Rhodes KJ, and Trimmer JS (1996) Identification of a cytoplasmic domain important in the polarized expression and clustering of the Kv2.1 K+ channel. J Cell Biol 135:1619-1632

  • ↵30. Archer SL, Souil E, Dinh-Xuan AT, Schremmer B, Mercier JC, El Yaagoubi A, Nguyen-Huu L, Reeve HL, and Hampl V (1998) Molecular identification of the role of voltage-gated K+ channels, Kv1.5 and Kv2.1, in hypoxic pulmonary vasoconstriction and control of resting membrane potential in rat pulmonary artery myocytes. J Clin Invest 101:2319-2330

  • ↵31. MacDonald PE, Ha XF, Wang J, Smukler SR, Sun AM, Gaisano HY, Salapatek AM, Backx PH, and Wheeler MB (2001) Members of the Kv1 and Kv2 voltage-dependent K+ channel families regulate insulin secretion. Mol Endocrinol 15:1423-1435

  • ↵32. Michelakis ED, McMurtry MS, Wu XC, Dyck JR, Moudgil R, Hopkins TA, Lopaschuk GD, Puttagunta L, Waite R, and Archer SL (2002) Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: role of increased expression and activity of voltage-gated potassium channels. Circulation 105:244-250

  • ↵33. UniGene Cluster Hs0.84244; OMIM no. 600397

  • ↵34. Iwasa H, Kurabayashi M, Nagai R, Nakamura Y, and Tanaka, T (2001) Multiple single-nucleotide polymorphisms (SNPs) in the Japanese population in six candidate genes for long QT syndrome. J Hum Genet 46:158-162

  • ↵35. Albrecht B, Lorra C, Stocker M, and Pongs O (1993) Cloning and characterization of a human delayed rectifier potassium channel gene. Receptor Channels 1:99-110