title: Neuronal voltage-gated K+ (Kv) channels function in macromolecular complexes.
abstract: Considerable evidence indicates that native neuronal voltage-gated K+ (Kv) currents reflect the functioning of macromolecular Kv channel complexes, composed of pore-forming (α)-subunits, cytosolic and transmembrane accessory subunits, together with regulatory and scaffolding proteins. The individual components of these macromolecular complexes appear to influence the stability, the trafficking, the localization and/or the biophysical properties of the channels. Recent studies suggest that Kv channel accessory subunits subserve multiple roles in the generation of native neuronal Kv channels. Additional recent findings suggest that Kv channel accessory subunits can respond to changes in intracellular Ca(2+) or metabolism and thereby integrate signaling pathways to regulate Kv channel expression and properties. Although studies in heterologous cells have provided important insights into the effects of accessory subunits on Kv channel expression/properties, it has become increasingly clear that experiments in neurons are required to define the physiological roles of Kv channel accessory and associated proteins. A number of technological and experimental hurdles remain that must be overcome in the design, execution and interpretation of experiments aimed at detailing the functional roles of accessory subunits and associated proteins in the generation of native neuronal Kv channels. With the increasing association of altered Kv channel functioning with neurological disorders, the potential impact of these efforts is clear.
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, St. Louis, MO 63110, United States.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Norris
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Foeger
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Nerbonne
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D046912:Multiprotein Complexes / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D021122:Protein Subunits / Q000502:physiology; D015398:Signal Transduction
chemical_list: D046912:Multiprotein Complexes; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D002118:Calcium
references.citation: J Neurosci. 2003 Oct 8;23(27):9097-106
references.pmid: 14534243
references.citation: J Neurosci. 2002 Dec 1;22(23):10123-33
references.pmid: 12451113
references.citation: Prog Neurobiol. 2009 Jan 12;87(1):41-57
references.pmid: 18952142
references.citation: Nature. 1997 Jun 26;387(6636):869-75
references.pmid: 9202119
references.citation: J Biol Chem. 2004 Oct 15;279(42):43847-53
references.pmid: 15292205
references.citation: J Neurogenet. 2008;22(2):1-13
references.pmid: 18428031
references.citation: J Neurol Neurosurg Psychiatry. 2008 Sep;79(9):1085
references.pmid: 18708572
references.citation: Trends Cardiovasc Med. 1999 Nov;9(8):253-8
references.pmid: 11094335
references.citation: J Biol Chem. 2002 Apr 12;277(15):13219-28
references.pmid: 11825900
references.citation: Neuron. 1996 Apr;16(4):843-52
references.pmid: 8608002
references.citation: Nat Med. 1998 Oct;4(10):1177-81
references.pmid: 9771752
references.citation: J Neurosci. 2010 Oct 13;30(41):13644-55
references.pmid: 20943905
references.citation: Learn Mem. 2009 Feb 17;16(3):167-77
references.pmid: 19223600
references.citation: Nat Genet. 1994 Oct;8(2):136-40
references.pmid: 7842011
references.citation: Channels (Austin). 2009 Jul-Aug;3(4):284-94
references.pmid: 19713751
references.citation: J Neurobiol. 2005 Jul;64(1):75-90
references.pmid: 15884003
references.citation: J Neurosci. 2006 Nov 22;26(47):12143-51
references.pmid: 17122039
references.citation: Mol Neurobiol. 2002 Feb;25(1):51-66
references.pmid: 11890457
references.citation: Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15119-23
references.pmid: 9005448
references.citation: Nat Rev Neurosci. 2007 Mar;8(3):182-93
references.pmid: 17311005
references.citation: Nat Genet. 2008 Jan;40(1):29-31
references.pmid: 18084291
references.citation: J Biol Chem. 2003 Sep 19;278(38):36445-54
references.pmid: 12829703
references.citation: Neuron. 2006 Apr 6;50(1):89-100
references.pmid: 16600858
references.citation: J Neurosci. 2004 Apr 7;24(14):3643-54
references.pmid: 15071113
references.citation: Nat Rev Neurosci. 2006 Jul;7(7):548-62
references.pmid: 16791144
references.citation: Physiol Rev. 2010 Apr;90(2):559-605
references.pmid: 20393194
references.citation: FEBS Lett. 1999 Jun 4;452(1-2):31-5
references.pmid: 10376673
references.citation: J Gen Physiol. 1999 Jun;113(6):897-907
references.pmid: 10352037
references.citation: FASEB J. 2001 Mar;15(3):589-91
references.pmid: 11259376
references.citation: Circ Res. 2009 Jun 19;104(12):1382-9
references.pmid: 19461043
references.citation: J Neurosci. 2003 Nov 12;23(32):10445-53
references.pmid: 14614103
references.citation: Nature. 1994 May 26;369(6478):289-94
references.pmid: 8183366
references.citation: Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6763-7
references.pmid: 7542775
references.citation: Biochemistry. 2008 Feb 26;47(8):2252-64
references.pmid: 18201103
references.citation: Am J Hum Genet. 2008 Feb;82(2):477-88
references.pmid: 18252227
references.citation: Science. 2003 Aug 1;301(5633):646-9
references.pmid: 12893943
references.citation: Nat Genet. 2002 Mar;30(3):335-41
references.pmid: 11810107
references.citation: Ann N Y Acad Sci. 1999 Apr 30;868:233-85
references.pmid: 10414301
references.citation: Biochem J. 2009 Feb 1;417(3):705-15
references.pmid: 18795890
references.citation: J Biol Chem. 2007 Jan 12;282(2):1205-15
references.pmid: 17102134
references.citation: Nature. 1999 Mar 4;398(6722):80-4
references.pmid: 10078534
references.citation: J Biol Chem. 2001 Jan 5;276(1):738-41
references.pmid: 11024060
references.citation: J Neurophysiol. 2008 Oct;100(4):1835-47
references.pmid: 18667548
references.citation: J Neurosci. 2010 Jun 2;30(22):7575-86
references.pmid: 20519532
references.citation: J Biol Chem. 1998 Dec 25;273(52):35095-101
references.pmid: 9857044
references.citation: J Biol Chem. 2006 Jun 2;281(22):15194-200
references.pmid: 16569641
references.citation: EMBO J. 2001 Oct 15;20(20):5715-24
references.pmid: 11598014
references.citation: Physiol Rev. 2010 Apr;90(2):755-96
references.pmid: 20393197
references.citation: Nat Neurosci. 2010 Mar;13(3):333-7
references.pmid: 20154682
references.citation: Neuron. 2006 Dec 7;52(5):803-16
references.pmid: 17145502
references.citation: Channels (Austin). 2010 May-Jun;4(3):163-7
references.pmid: 20458163
references.citation: FEBS Lett. 2003 Jul 17;547(1-3):162-4
references.pmid: 12860406
references.citation: J Neurosci. 1996 Aug 15;16(16):4846-60
references.pmid: 8756417
references.citation: Nature. 2008 Mar 27;452(7186):436-41
references.pmid: 18368112
references.citation: Neurology. 2009 Mar 31;72(13):1184-5
references.pmid: 19332697
references.citation: J Biol Chem. 2001 Feb 16;276(7):4839-44
references.pmid: 11087728
references.citation: Trends Biochem Sci. 2006 Jul;31(7):411-9
references.pmid: 16781869
references.citation: Nat Struct Mol Biol. 2006 Nov;13(11):987-95
references.pmid: 17057713
references.citation: J Biol Chem. 2002 Apr 26;277(17):14965-75
references.pmid: 11847232
references.citation: J Mol Cell Cardiol. 2005 Jul;39(1):121-32
references.pmid: 15878168
references.citation: J Neurochem. 2004 Feb;88(3):604-11
references.pmid: 14720210
references.citation: J Neurosci. 2000 Dec 1;20(23):8736-44
references.pmid: 11102480
references.citation: Cell. 1999 Jun 25;97(7):943-52
references.pmid: 10399921
references.citation: J Neurosci. 2003 Jun 15;23(12):4798-802
references.pmid: 12832499
references.citation: J Physiol. 2008 Dec 1;586(23):5609-23
references.pmid: 18845608