title: Signaling complexes of voltage-gated sodium and calcium channels.
abstract: Membrane depolarization and intracellular Ca(2+) transients generated by activation of voltage-gated Na+ and Ca(2+) channels are local signals, which initiate physiological processes such as action potential conduction, synaptic transmission, and excitation-contraction coupling. Targeting of effector proteins and regulatory proteins to ion channels is an important mechanism to ensure speed, specificity, and precise regulation of signaling events in response to local stimuli. This article reviews experimental results showing that Na+ and Ca(2+) channels form local signaling complexes, in which effector proteins, anchoring proteins, and regulatory proteins interact directly with ion channels. The intracellular domains of these channels serve as signaling platforms, mediating their participation in intracellular signaling processes. These protein-protein interactions are important for regulation of cellular plasticity through modulation of Na+ channel function in brain neurons, for short-term synaptic plasticity through modulation of presynaptic Ca(V)2 channels, and for the fight-or-flight response through regulation of postsynaptic Ca(V)1 channels in skeletal and cardiac muscle. These localized signaling complexes are essential for normal function and regulation of electrical excitability, synaptic transmission, and excitation-contraction coupling.
authors.affiliation: Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98195-7280, United States. wcatt@u.washington.edu
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating; D046912:Multiprotein Complexes / Q000502:physiology; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D046912:Multiprotein Complexes; D015222:Sodium Channels
references.citation: Neuron. 1997 Jul;19(1):185-96
references.pmid: 9247274
references.citation: EMBO J. 2001 Apr 2;20(7):1651-62
references.pmid: 11285229
references.citation: Nat New Biol. 1973 Sep 26;245(143):120-2
references.pmid: 4355672
references.citation: J Neurosci. 1997 Aug 15;17(16):6086-93
references.pmid: 9236220
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2283-8
references.pmid: 20133873
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11492-6
references.pmid: 7972090
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):341-6
references.pmid: 18162541
references.citation: Recept Channels. 1998;6(2):89-98
references.pmid: 9932286
references.citation: Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7363-8
references.pmid: 8692999
references.citation: Mol Cell Biochem. 1996 Oct-Nov;163-164:99-106
references.pmid: 8974044
references.citation: Proc Natl Acad Sci U S A. 1987 Aug;84(15):5478-82
references.pmid: 2440051
references.citation: J Neurosci. 2007 Oct 24;27(43):11543-51
references.pmid: 17959797
references.citation: Proc Natl Acad Sci U S A. 1985 Apr;82(8):2528-32
references.pmid: 2581248
references.citation: Nature. 1993 Jan 14;361(6408):165-8
references.pmid: 8380626
references.citation: J Biol Chem. 1982 Jul 25;257(14):7918-21
references.pmid: 6282861
references.citation: Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1512-6
references.pmid: 9037084
references.citation: Physiol Rev. 1994 Apr;74(2):365-507
references.pmid: 8171118
references.citation: Nature. 1999 May 13;399(6732):155-9
references.pmid: 10335845
references.citation: Mol Cell Neurosci. 2001 Nov;18(5):570-80
references.pmid: 11922146
references.citation: Science. 1997 Dec 19;278(5346):2075-80
references.pmid: 9405336
references.citation: Nature. 1996 Feb 1;379(6564):451-4
references.pmid: 8559250
references.citation: Neuron. 2001 Sep 27;31(6):973-85
references.pmid: 11580897
references.citation: Biochemistry. 1996 Aug 13;35(32):10392-402
references.pmid: 8756695
references.citation: FEBS Lett. 1997 Mar 10;404(2-3):203-7
references.pmid: 9119064
references.citation: Nat Neurosci. 2000 May;3(5):437-44
references.pmid: 10769382
references.citation: J Neurosci. 1997 Feb 15;17(4):1243-55
references.pmid: 9006969
references.citation: Mol Cell Neurosci. 2002 Sep;21(1):63-80
references.pmid: 12359152
references.citation: Biochemistry. 1997 Aug 5;36(31):9605-15
references.pmid: 9236007
references.citation: J Biol Chem. 1997 Sep 19;272(38):23637-44
references.pmid: 9295304
references.citation: J Neurosci. 1997 Aug 1;17(15):5772-81
references.pmid: 9221775
references.citation: Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10778-82
references.pmid: 1720551
references.citation: EMBO J. 1998 Apr 15;17(8):2261-72
references.pmid: 9545239
references.citation: Nature. 1996 Mar 21;380(6571):255-8
references.pmid: 8637575
references.citation: J Biol Chem. 1993 Sep 15;268(26):19451-7
references.pmid: 8396138
references.citation: J Mol Cell Cardiol. 1986 Jul;18(7):691-710
references.pmid: 2427730
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):14950-7
references.pmid: 20668236
references.citation: Sci Signal. 2010 Sep 28;3(141):ra70
references.pmid: 20876873
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13093-8
references.pmid: 14569017
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16059-64
references.pmid: 14673106
references.citation: Mol Cell Neurosci. 2005 Jan;28(1):1-17
references.pmid: 15607937
references.citation: Neuron. 1994 Dec;13(6):1303-13
references.pmid: 7993624
references.citation: Nature. 1995 Dec 7;378(6557):623-6
references.pmid: 8524397
references.citation: J Biol Chem. 2001 Jun 15;276(24):21089-97
references.pmid: 11274161
references.citation: Nature. 1996 Mar 7;380(6569):72-5
references.pmid: 8598910
references.citation: Neuron. 1996 Oct;17(4):781-8
references.pmid: 8893034
references.citation: Mol Endocrinol. 1994 Jan;8(1):5-11
references.pmid: 8152430
references.citation: J Neurosci. 1997 Sep 15;17(18):6929-38
references.pmid: 9278528
references.citation: Annu Rev Cell Dev Biol. 2000;16:521-55
references.pmid: 11031246
references.citation: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5405-10
references.pmid: 9144250
references.citation: Nat Rev Neurosci. 2001 Jun;2(6):397-407
references.pmid: 11389473
references.citation: Adv Second Messenger Phosphoprotein Res. 1999;33:131-51
references.pmid: 10218117
references.citation: J Neurosci. 2005 Jul 27;25(30):7071-80
references.pmid: 16049184
references.citation: Nature. 1995 Jun 22;375(6533):645-53
references.pmid: 7791897
references.citation: J Neurosci. 2008 Mar 19;28(12):3246-56
references.pmid: 18354028
references.citation: J Cell Biol. 2001 Jul 23;154(2):427-34
references.pmid: 11470829
references.citation: Neuron. 1996 Nov;17(5):991-1003
references.pmid: 8938130
references.citation: J Biol Chem. 2002 Feb 8;277(6):4079-87
references.pmid: 11733497
references.citation: Trends Neurosci. 1994 Dec;17(12):531-6
references.pmid: 7532338
references.citation: Biochemistry. 1996 Jul 23;35(29):9400-6
references.pmid: 8755718
references.citation: J Biol Chem. 2000 Mar 24;275(12):8556-63
references.pmid: 10722694
references.citation: J Neurosci. 2007 Oct 24;27(43):11533-42
references.pmid: 17959796
references.citation: Eur J Biochem. 1983 Sep 1;135(1):131-42
references.pmid: 6309517
references.citation: J Neurosci. 1997 Sep 1;17(17):6647-56
references.pmid: 9254677
references.citation: Pflugers Arch. 1986 Feb;406(2):104-11
references.pmid: 2421234
references.citation: J Biol Chem. 1993 Dec 25;268(36):27355-62
references.pmid: 8262976
references.citation: J Physiol. 1998 Nov 1;512 ( Pt 3):723-9
references.pmid: 9769416
references.citation: EMBO J. 1996 Aug 15;15(16):4100-10
references.pmid: 8861939
references.citation: Adv Exp Med Biol. 2002;514:303-17
references.pmid: 12596929
references.citation: Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8866-71
references.pmid: 9238069
references.citation: Cold Spring Harb Symp Quant Biol. 1990;55:1-7
references.pmid: 1966760
references.citation: J Neurosci. 1999 Jul 1;19(13):5301-10
references.pmid: 10377341
references.citation: J Neurosci. 1999 Aug 15;19(16):6855-64
references.pmid: 10436043
references.citation: J Biol Chem. 1984 Jul 10;259(13):8210-8
references.pmid: 6330103
references.citation: Science. 1993 Sep 10;261(5127):1439-42
references.pmid: 8396273
references.citation: Nat Neurosci. 2002 Mar;5(3):210-7
references.pmid: 11865310
references.citation: J Neurosci. 2000 Feb 1;20(3):889-98
references.pmid: 10648693
references.citation: Science. 2002 Mar 22;295(5563):2276-9
references.pmid: 11910115
references.citation: J Biol Chem. 1987 Dec 25;262(36):17530-5
references.pmid: 2447073
references.citation: J Neurosci. 1996 Mar 15;16(6):1965-74
references.pmid: 8604040
references.citation: Nature. 1989 Jul 13;340(6229):153-6
references.pmid: 2567963
references.citation: J Physiol. 1998 Nov 15;513 ( Pt 1):149-55
references.pmid: 9782166
references.citation: Eur J Biochem. 1986 Nov 17;161(1):217-24
references.pmid: 3023084
references.citation: EMBO J. 1997 Aug 1;16(15):4591-6
references.pmid: 9303303
references.citation: J Physiol. 1977 Jan;264(1):49-62
references.pmid: 839456
references.citation: Nature. 1983 Feb 17-23;301(5901):569-74
references.pmid: 6131381
references.citation: J Biol Chem. 1992 Aug 15;267(23):16100-5
references.pmid: 1322891
references.citation: J Neurosci. 1999 Sep 1;19(17):RC21
references.pmid: 10460275
references.citation: Neuron. 2006 Feb 2;49(3):409-20
references.pmid: 16446144
references.citation: Nat Neurosci. 2003 Oct;6(10):1031-8
references.pmid: 12947410
references.citation: Nature. 1997 Jan 30;385(6615):442-6
references.pmid: 9009192
references.citation: Nat Neurosci. 1999 Nov;2(11):939-41
references.pmid: 10526329
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15753-7
references.pmid: 9861042
references.citation: Nature. 1982 Aug 5;298(5874):576-8
references.pmid: 6285199
references.citation: J Neurosci. 2000 Sep 15;20(18):6830-8
references.pmid: 10995827
references.citation: J Biol Chem. 1989 Aug 25;264(24):14220-4
references.pmid: 2547790
references.citation: J Biol Chem. 1995 Feb 3;270(5):1971-4
references.pmid: 7836421
references.citation: J Neurosci. 1998 Jul 1;18(13):4815-24
references.pmid: 9634547
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5274-9
references.pmid: 15793008
references.citation: J Physiol. 1997 Feb 1;498 ( Pt 3):601-10
references.pmid: 9051573
references.citation: J Neurosci. 2007 Jan 10;27(2):265-9
references.pmid: 17215385
references.citation: J Biol Chem. 1997 Mar 7;272(10):6297-302
references.pmid: 9045648
references.citation: Neuron. 2008 Jan 24;57(2):210-6
references.pmid: 18215619
references.citation: Neuron. 2003 Aug 28;39(5):793-806
references.pmid: 12948446
references.citation: Proc Natl Acad Sci U S A. 1989 Nov;86(21):8585-9
references.pmid: 2554320
references.citation: Neuron. 1992 Jun;8(6):1151-9
references.pmid: 1319185
references.citation: J Cell Biol. 1998 Nov 30;143(5):1295-304
references.pmid: 9832557
references.citation: Nature. 1996 Mar 21;380(6571):258-62
references.pmid: 8637576
references.citation: J Neurosci. 1997 Feb 15;17(4):1330-8
references.pmid: 9006976
references.citation: J Neurosci. 2003 Aug 20;23(20):7577-85
references.pmid: 12930796
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5187-92
references.pmid: 17360357
references.citation: Nature. 1997 Jan 30;385(6615):446-50
references.pmid: 9009193
references.citation: J Neurosci. 2001 Oct 1;21(19):7517-25
references.pmid: 11567041
references.citation: J Biol Chem. 1995 Jul 7;270(27):16371-7
references.pmid: 7608207
references.citation: Biochim Biophys Acta. 1994 Dec 30;1224(3):467-79
references.pmid: 7803506
references.citation: Nature. 1993 Jul 15;364(6434):240-3
references.pmid: 8391648
references.citation: J Biol Chem. 1994 Jan 21;269(3):1635-40
references.pmid: 7507480
references.citation: J Neurosci. 1997 Oct 1;17(19):7330-8
references.pmid: 9295379
references.citation: Neuron. 1998 May;20(5):1017-26
references.pmid: 9620705
references.citation: Nature. 2001 May 24;411(6836):484-9
references.pmid: 11373682
references.citation: J Biol Chem. 1987 Sep 15;262(26):12735-44
references.pmid: 2442166
references.citation: Nature. 1999 Oct 21;401(6755):800-4
references.pmid: 10548106
references.citation: J Biol Chem. 1999 Sep 10;274(37):26511-7
references.pmid: 10473612
references.citation: Biochemistry. 1984 May 8;23(10):2113-8
references.pmid: 6329263
references.citation: J Physiol. 1952 Aug;117(4):500-44
references.pmid: 12991237
references.citation: J Biol Chem. 2000 Apr 14;275(15):11383-8
references.pmid: 10753953
references.citation: J Physiol. 2006 Oct 1;576(Pt 1):87-102
references.pmid: 16809371
references.citation: J Biochem Mol Biol. 2007 May 31;40(3):302-14
references.pmid: 17562281
references.citation: Neuron. 1998 Apr;20(4):797-807
references.pmid: 9581770
references.citation: Neuron. 1993 Aug;11(2):305-20
references.pmid: 8102534
references.citation: Neuron. 2008 Sep 25;59(6):882-901
references.pmid: 18817729
references.citation: Mol Pharmacol. 2004 Sep;66(3):761-9
references.pmid: 15322269
references.citation: J Neurosci. 1998 Nov 15;18(22):9163-70
references.pmid: 9801356
references.citation: J Neurosci. 2005 Jul 27;25(30):7062-70
references.pmid: 16049183