8sd3

Structural highlights

Function

KCNB1_RAT Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:10024359, PubMed:10618149, PubMed:12451110, PubMed:17379638, PubMed:19276663, PubMed:23878373). Also plays a role in the regulation of exocytosis independently of its electrical function (PubMed:20484665). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:2770868, PubMed:2206531, PubMed:1875913, PubMed:8083226, PubMed:8978827, PubMed:9351973, PubMed:9565597, PubMed:12560340). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:20202934). Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (PubMed:8670833, PubMed:8980147, PubMed:9362476, PubMed:9079713, PubMed:9305895, PubMed:9696692). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (PubMed:9362476). Channel properties are also modulated by cytoplasmic ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (PubMed:12954870, PubMed:19219384). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Major contributor to the slowly inactivating delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle cells (PubMed:9362476, PubMed:9616203, PubMed:10024359, PubMed:10414968, PubMed:10618149, PubMed:11463864, PubMed:12451110, PubMed:12127166, PubMed:12403834, PubMed:12621036, PubMed:12807875, PubMed:12832499, PubMed:12954870, PubMed:15322114, PubMed:15195093, PubMed:16407566, PubMed:17301173, PubMed:17379638, PubMed:18463252, PubMed:18167541, PubMed:19276663, PubMed:20484665, PubMed:21518833, PubMed:22411134, PubMed:23878373). Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation (PubMed:10618149, PubMed:12451110, PubMed:16319318, PubMed:17379638, PubMed:19276663, PubMed:23878373, PubMed:16917065). Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (By similarity). Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion (PubMed:11463864). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells (PubMed:9616203). May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval (By similarity). Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury (PubMed:12832499, PubMed:16273079, PubMed:17360683, PubMed:19077057, PubMed:19622611, PubMed:24928958). May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (PubMed:16319318). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (By similarity). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner (PubMed:11463864, PubMed:17301173, PubMed:18167541, PubMed:20484665, PubMed:22411134).[UniProtKB:Q03717]^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47]}

References

1. ↑ Murakoshi H, Trimmer JS. Identification of the Kv2.1 K+ channel as a major component of the delayed rectifier K+ current in rat hippocampal neurons. J Neurosci. 1999 Mar 1;19(5):1728-35. PMID:10024359 doi:10.1523/JNEUROSCI.19-05-01728.1999
2. ↑ Baranauskas G, Tkatch T, Surmeier DJ. Delayed rectifier currents in rat globus pallidus neurons are attributable to Kv2.1 and Kv3.1/3.2 K(+) channels. J Neurosci. 1999 Aug 1;19(15):6394-404. PMID:10414968 doi:10.1523/JNEUROSCI.19-15-06394.1999
3. ↑ Du J, Haak LL, Phillips-Tansey E, Russell JT, McBain CJ. Frequency-dependent regulation of rat hippocampal somato-dendritic excitability by the K+ channel subunit Kv2.1. J Physiol. 2000 Jan 1;522 Pt 1(Pt 1):19-31. PMID:10618149 doi:10.1111/j.1469-7793.2000.t01-2-00019.xm
4. ↑ MacDonald PE, Ha XF, Wang J, Smukler SR, Sun AM, Gaisano HY, Salapatek AM, Backx PH, Wheeler MB. Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion. Mol Endocrinol. 2001 Aug;15(8):1423-35. PMID:11463864 doi:10.1210/mend.15.8.0685
5. ↑ Lu Y, Hanna ST, Tang G, Wang R. Contributions of Kv1.2, Kv1.5 and Kv2.1 subunits to the native delayed rectifier K(+) current in rat mesenteric artery smooth muscle cells. Life Sci. 2002 Aug 9;71(12):1465-73. PMID:12127166 doi:10.1016/s0024-3205(02)01922-7
6. ↑ MacDonald PE, Wang G, Tsuk S, Dodo C, Kang Y, Tang L, Wheeler MB, Cattral MS, Lakey JR, Salapatek AM, Lotan I, Gaisano HY. Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-dependent K(+) channels in neuroendocrine islet beta-cells through an interaction with the channel N terminus. Mol Endocrinol. 2002 Nov;16(11):2452-61. PMID:12403834 doi:10.1210/me.2002-0058
7. ↑ Malin SA, Nerbonne JM. Delayed rectifier K+ currents, IK, are encoded by Kv2 alpha-subunits and regulate tonic firing in mammalian sympathetic neurons. J Neurosci. 2002 Dec 1;22(23):10094-105. PMID:12451110 doi:10.1523/JNEUROSCI.22-23-10094.2002
8. ↑ Ju M, Stevens L, Leadbitter E, Wray D. The Roles of N potassium channel. J Biol Chem. 2003 Apr 11;278(15):12769-78. PMID:12560340 doi:10.1074/jbc.M212973200
9. ↑ Leung YM, Kang Y, Gao X, Xia F, Xie H, Sheu L, Tsuk S, Lotan I, Tsushima RG, Gaisano HY. Syntaxin 1A binds to the cytoplasmic C terminus of Kv2.1 to regulate channel gating and trafficking. J Biol Chem. 2003 May 9;278(19):17532-8. PMID:12621036 doi:10.1074/jbc.M213088200
10. ↑ Michaelevski I, Chikvashvili D, Tsuk S, Singer-Lahat D, Kang Y, Linial M, Gaisano HY, Fili O, Lotan I. Direct interaction of target SNAREs with the Kv2.1 channel. Modal regulation of channel activation and inactivation gating. J Biol Chem. 2003 Sep 5;278(36):34320-30. PMID:12807875 doi:10.1074/jbc.M304943200
11. ↑ Pal S, Hartnett KA, Nerbonne JM, Levitan ES, Aizenman E. Mediation of neuronal apoptosis by Kv2.1-encoded potassium channels. J Neurosci. 2003 Jun 15;23(12):4798-802. PMID:12832499 doi:10.1523/JNEUROSCI.23-12-04798.2003
12. ↑ McCrossan ZA, Lewis A, Panaghie G, Jordan PN, Christini DJ, Lerner DJ, Abbott GW. MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels in mammalian brain. J Neurosci. 2003 Sep 3;23(22):8077-91. PMID:12954870
13. ↑ Misonou H, Mohapatra DP, Park EW, Leung V, Zhen D, Misonou K, Anderson AE, Trimmer JS. Regulation of ion channel localization and phosphorylation by neuronal activity. Nat Neurosci. 2004 Jul;7(7):711-8. PMID:15195093 doi:10.1038/nn1260
14. ↑ Amberg GC, Rossow CF, Navedo MF, Santana LF. NFATc3 regulates Kv2.1 expression in arterial smooth muscle. J Biol Chem. 2004 Nov 5;279(45):47326-34. PMID:15322114 doi:10.1074/jbc.M408789200
15. ↑ Pal SK, Takimoto K, Aizenman E, Levitan ES. Apoptotic surface delivery of K+ channels. Cell Death Differ. 2006 Apr;13(4):661-7. PMID:16273079 doi:10.1038/sj.cdd.4401792
16. ↑ Misonou H, Mohapatra DP, Menegola M, Trimmer JS. Calcium channel regulates neuronal excitability in response to ischemia. J Neurosci. 2005 Nov 30;25(48):11184-93. PMID:16319318 doi:10.1523/JNEUROSCI.3370-05.2005
17. ↑ Mohapatra DP, Trimmer JS. The Kv2.1 C terminus can autonomously transfer Kv2.1-like phosphorylation-dependent localization, voltage-dependent gating, and muscarinic modulation to diverse Kv channels. J Neurosci. 2006 Jan 11;26(2):685-95. PMID:16407566 doi:10.1523/JNEUROSCI.4620-05.2006
18. ↑ Park KS, Mohapatra DP, Misonou H, Trimmer JS. Graded regulation of the Kv2.1 potassium channel by variable phosphorylation. Science. 2006 Aug 18;313(5789):976-9. PMID:16917065 doi:10.1126/science.1124254
19. ↑ Singer-Lahat D, Sheinin A, Chikvashvili D, Tsuk S, Greitzer D, Friedrich R, Feinshreiber L, Ashery U, Benveniste M, Levitan ES, Lotan I. K+ channel facilitation of exocytosis by dynamic interaction with syntaxin. J Neurosci. 2007 Feb 14;27(7):1651-8. PMID:17301173 doi:10.1523/JNEUROSCI.4006-06.2007
20. ↑ Redman PT, He K, Hartnett KA, Jefferson BS, Hu L, Rosenberg PA, Levitan ES, Aizenman E. Apoptotic surge of potassium currents is mediated by p38 phosphorylation of Kv2.1. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3568-73. PMID:17360683 doi:10.1073/pnas.0610159104
21. ↑ Guan D, Tkatch T, Surmeier DJ, Armstrong WE, Foehring RC. Kv2 subunits underlie slowly inactivating potassium current in rat neocortical pyramidal neurons. J Physiol. 2007 Jun 15;581(Pt 3):941-60. PMID:17379638 doi:10.1113/jphysiol.2007.128454
22. ↑ Singer-Lahat D, Chikvashvili D, Lotan I. Direct interaction of endogenous Kv channels with syntaxin enhances exocytosis by neuroendocrine cells. PLoS One. 2008 Jan 2;3(1):e1381. PMID:18167541 doi:10.1371/journal.pone.0001381
23. ↑ Mohapatra DP, Siino DF, Trimmer JS. Interdomain cytoplasmic interactions govern the intracellular trafficking, gating, and modulation of the Kv2.1 channel. J Neurosci. 2008 May 7;28(19):4982-94. PMID:18463252 doi:10.1523/JNEUROSCI.0186-08.2008
24. ↑ Taglialatela M, Vandongen AM, Drewe JA, Joho RH, Brown AM, Kirsch GE. Patterns of internal and external tetraethylammonium block in four homologous K+ channels. Mol Pharmacol. 1991 Aug;40(2):299-307 PMID:1875913
25. ↑ Yao H, Zhou K, Yan D, Li M, Wang Y. The Kv2.1 channels mediate neuronal apoptosis induced by excitotoxicity. J Neurochem. 2009 Feb;108(4):909-19. PMID:19077057 doi:10.1111/j.1471-4159.2008.05834.x
26. ↑ McCrossan ZA, Roepke TK, Lewis A, Panaghie G, Abbott GW. Regulation of the Kv2.1 potassium channel by MinK and MiRP1. J Membr Biol. 2009 Mar;228(1):1-14. PMID:19219384 doi:10.1007/s00232-009-9154-8
27. ↑ Mohapatra DP, Misonou H, Pan SJ, Held JE, Surmeier DJ, Trimmer JS. Regulation of intrinsic excitability in hippocampal neurons by activity-dependent modulation of the KV2.1 potassium channel. Channels (Austin). 2009 Jan-Feb;3(1):46-56. PMID:19276663 doi:10.4161/chan.3.1.7655
28. ↑ Redman PT, Hartnett KA, Aras MA, Levitan ES, Aizenman E. Regulation of apoptotic potassium currents by coordinated zinc-dependent signalling. J Physiol. 2009 Sep 15;587(Pt 18):4393-404. PMID:19622611 doi:10.1113/jphysiol.2009.176321
29. ↑ Kihira Y, Hermanstyne TO, Misonou H. Formation of heteromeric Kv2 channels in mammalian brain neurons. J Biol Chem. 2010 May 14;285(20):15048-15055. PMID:20202934 doi:10.1074/jbc.M109.074260
30. ↑ Feinshreiber L, Singer-Lahat D, Friedrich R, Matti U, Sheinin A, Yizhar O, Nachman R, Chikvashvili D, Rettig J, Ashery U, Lotan I. Non-conducting function of the Kv2.1 channel enables it to recruit vesicles for release in neuroendocrine and nerve cells. J Cell Sci. 2010 Jun 1;123(Pt 11):1940-7. PMID:20484665 doi:10.1242/jcs.063719
31. ↑ Plant LD, Dowdell EJ, Dementieva IS, Marks JD, Goldstein SA. SUMO modification of cell surface Kv2.1 potassium channels regulates the activity of rat hippocampal neurons. J Gen Physiol. 2011 May;137(5):441-54. PMID:21518833 doi:10.1085/jgp.201110604
32. ↑ VanDongen AM, Frech GC, Drewe JA, Joho RH, Brown AM. Alteration and restoration of K+ channel function by deletions at the N C-termini. Neuron. 1990 Oct;5(4):433-43. PMID:2206531 doi:10.1016/0896-6273(90)90082-q
33. ↑ Dai XQ, Manning Fox JE, Chikvashvili D, Casimir M, Plummer G, Hajmrle C, Spigelman AF, Kin T, Singer-Lahat D, Kang Y, Shapiro AM, Gaisano HY, Lotan I, Macdonald PE. The voltage-dependent potassium channel subunit Kv2.1 regulates insulin secretion from rodent and human islets independently of its electrical function. Diabetologia. 2012 Jun;55(6):1709-20. PMID:22411134 doi:10.1007/s00125-012-2512-6
34. ↑ Guan D, Armstrong WE, Foehring RC. Kv2 channels regulate firing rate in pyramidal neurons from rat sensorimotor cortex. J Physiol. 2013 Oct 1;591(19):4807-25. PMID:23878373 doi:10.1113/jphysiol.2013.257253
35. ↑ McCord MC, Kullmann PH, He K, Hartnett KA, Horn JP, Lotan I, Aizenman E. Syntaxin-binding domain of Kv2.1 is essential for the expression of apoptotic K+ currents. J Physiol. 2014 Aug 15;592(16):3511-21. PMID:24928958 doi:10.1113/jphysiol.2014.276964
36. ↑ Frech GC, VanDongen AM, Schuster G, Brown AM, Joho RH. A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning. Nature. 1989 Aug 24;340(6235):642-5. PMID:2770868 doi:10.1038/340642a0
37. ↑ Shi G, Kleinklaus AK, Marrion NV, Trimmer JS. Properties of Kv2.1 K+ channels expressed in transfected mammalian cells. J Biol Chem. 1994 Sep 16;269(37):23204-11 PMID:8083226
38. ↑ Hugnot JP, Salinas M, Lesage F, Guillemare E, de Weille J, Heurteaux C, Mattéi MG, Lazdunski M. Kv8.1, a new neuronal potassium channel subunit with specific inhibitory properties towards Shab and Shaw channels. EMBO J. 1996 Jul 1;15(13):3322-31 PMID:8670833
39. ↑ Scannevin RH, Murakoshi H, Rhodes KJ, Trimmer JS. Identification of a cytoplasmic domain important in the polarized expression and clustering of the Kv2.1 K+ channel. J Cell Biol. 1996 Dec;135(6 Pt 1):1619-32. PMID:8978827 doi:10.1083/jcb.135.6.1619
40. ↑ Post MA, Kirsch GE, Brown AM. Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and express a novel current. FEBS Lett. 1996 Dec 9;399(1-2):177-82. PMID:8980147 doi:10.1016/s0014-5793(96)01316-6
41. ↑ Salinas M, de Weille J, Guillemare E, Lazdunski M, Hugnot JP. Modes of regulation of shab K+ channel activity by the Kv8.1 subunit. J Biol Chem. 1997 Mar 28;272(13):8774-80. PMID:9079713 doi:10.1074/jbc.272.13.8774
42. ↑ Salinas M, Duprat F, Heurteaux C, Hugnot JP, Lazdunski M. New modulatory alpha subunits for mammalian Shab K+ channels. J Biol Chem. 1997 Sep 26;272(39):24371-9. PMID:9305895 doi:10.1074/jbc.272.39.24371
43. ↑ Murakoshi H, Shi G, Scannevin RH, Trimmer JS. Phosphorylation of the Kv2.1 K+ channel alters voltage-dependent activation. Mol Pharmacol. 1997 Nov;52(5):821-8. PMID:9351973 doi:10.1124/mol.52.5.821
44. ↑ Patel AJ, Lazdunski M, Honoré E. Kv2.1/Kv9.3, a novel ATP-dependent delayed-rectifier K+ channel in oxygen-sensitive pulmonary artery myocytes. EMBO J. 1997 Nov 17;16(22):6615-25. PMID:9362476 doi:10.1093/emboj/16.22.6615
45. ↑ Wible BA, Yang Q, Kuryshev YA, Accili EA, Brown AM. Cloning and expression of a novel K+ channel regulatory protein, KChAP. J Biol Chem. 1998 May 8;273(19):11745-51. PMID:9565597 doi:10.1074/jbc.273.19.11745
46. ↑ Archer SL, Souil E, Dinh-Xuan AT, Schremmer B, Mercier JC, El Yaagoubi A, Nguyen-Huu L, Reeve HL, Hampl V. 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. 1998 Jun 1;101(11):2319-30. PMID:9616203 doi:10.1172/JCI333
47. ↑ Kramer JW, Post MA, Brown AM, Kirsch GE. Modulation of potassium channel gating by coexpression of Kv2.1 with regulatory Kv5.1 or Kv6.1 alpha-subunits. Am J Physiol. 1998 Jun;274(6):C1501-10. PMID:9696692 doi:10.1152/ajpcell.1998.274.6.C1501