title: BDNF induces calcium elevations associated with IBDNF, a nonselective cationic current mediated by TRPC channels.
abstract: Brain-derived neurotrophic factor (BDNF) has potent actions on hippocampal neurons, but the mechanisms that initiate its effects are poorly understood. We report here that localized BDNF application to apical dendrites of CA1 pyramidal neurons evoked transient elevations in intracellular Ca(2+) concentration, which are independent of membrane depolarization and activation of N-methyl-d-aspartate receptors (NMDAR). These Ca(2+) signals were always associated with I(BDNF), a slow and sustained nonselective cationic current mediated by transient receptor potential canonical (TRPC3) channels. BDNF-induced Ca(2+) elevations required functional Trk and inositol-tris-phosphate (IP(3)) receptors, full intracellular Ca(2+) stores as well as extracellular Ca(2+), suggesting the involvement of TRPC channels. Indeed, the TRPC channel inhibitor SKF-96365 prevented BDNF-induced Ca(2+) elevations and the associated I(BDNF). Thus TRPC channels emerge as novel mediators of BDNF-induced intracellular Ca(2+) elevations associated with sustained cationic membrane currents in hippocampal pyramidal neurons.
authors: Department of Neurobiology, Civitan International Research Center and McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.
authors: Michelle D
authors: MD
authors: Amaral
authors: Lucas
authors: L
authors: Pozzo-Miller
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D007093:Imidazoles; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D050052:TRPC Cation Channels; D020917:Receptor, trkA; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium
references: Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13279-86
references: 9371837
references: Annu Rev Neurosci. 1996;19:463-89
references: 8833451
references: J Neurosci. 2000 Apr 15;20(8):2809-16
references: 10751432
references: Neuron. 1999 Sep;24(1):261-73
references: 10677043
references: J Physiol. 2003 Dec 1;553(Pt 2):497-509
references: 14500767
references: Pharmacol Ther. 2007 Feb;113(2):394-409
references: 17118456
references: J Biol Chem. 1985 Mar 25;260(6):3440-50
references: 3838314
references: J Neurosci. 1996 May 15;16(10):3256-64
references: 8627363
references: Nat Neurosci. 2007 May;10(5):559-67
references: 17396124
references: Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1639-44
references: 11818568
references: Brain Res. 1997 Dec 19;778(2):318-28
references: 9459549
references: J Neurosci. 1998 Dec 15;18(24):10231-40
references: 9852560
references: Nature. 2002 Oct 17;419(6908):687-93
references: 12384689
references: Neuron. 1997 Sep;19(3):723-33
references: 9331361
references: J Neurosci. 2007 May 9;27(19):5179-89
references: 17494704
references: Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466-70
references: 2138778
references: Physiol Rev. 2005 Apr;85(2):757-810
references: 15788710
references: Prog Neurobiol. 2003 Apr;69(5):341-74
references: 12787574
references: J Neurochem. 1996 Jun;66(6):2279-86
references: 8632149
references: J Neurochem. 2001 Nov;79(3):522-30
references: 11701755
references: J Neurosci. 2001 Jun 15;21(12):4249-58
references: 11404410
references: Nature. 1999 Oct 28;401(6756):918-21
references: 10553907
references: Eur J Neurosci. 1997 Dec;9(12):2561-70
references: 9517461
references: Brain Res. 2006 Aug 9;1104(1):45-54
references: 16797499
references: J Neurophysiol. 1996 Jul;76(1):554-62
references: 8836243
references: J Neurosci. 2007 Jan 31;27(5):1097-105
references: 17267564
references: Neuroreport. 1993 Sep 30;4(12):1303-6
references: 7505114
references: Science. 2002 Mar 1;295(5560):1729-34
references: 11872844
references: Nat Neurosci. 1999 Apr;2(4):346-51
references: 10204541
references: J Neurosci Res. 2001 Oct 1;66(1):96-108
references: 11599006
references: J Biol Chem. 2002 Feb 22;277(8):6520-9
references: 11741947
references: Prog Neurobiol. 2005 Jun;76(2):99-125
references: 16099088
references: Cell Calcium. 2003 Oct-Nov;34(4-5):339-44
references: 12909080
references: Biochem J. 1990 Oct 15;271(2):515-22
references: 2173565
references: Nat Rev Neurosci. 2001 Jan;2(1):24-32
references: 11253356
references: Curr Opin Neurobiol. 1997 Jun;7(3):339-45
references: 9232803
references: J Neurophysiol. 1999 Mar;81(3):1404-11
references: 10085365
references: Int J Dev Neurosci. 2002 Jun-Aug;20(3-5):199-207
references: 12175855
references: Nature. 2005 Apr 14;434(7035):898-904
references: 15758951
references: J Biol Chem. 1998 Jan 2;273(1):133-42
references: 9417057
references: Neuron. 1995 Jun;14(6):1223-31
references: 7605633
references: J Neurochem. 1995 Nov;65(5):2241-50
references: 7595513
references: Behav Res Methods. 2007 May;39(2):175-91
references: 17695343
references: Nature. 2003 Dec 4;426(6966):517-24
references: 14654832
references: Neuroreport. 2005 Jun 21;16(9):977-80
references: 15931072
references: Learn Mem. 2003 Mar-Apr;10(2):86-98
references: 12663747
references: Learn Mem. 2002 Sep-Oct;9(5):224-37
references: 12359832
references: J Neurosci. 1995 Dec;15(12):8320-30
references: 8613765
references: J Neurochem. 1996 Sep;67(3):952-63
references: 8752100
references: J Neurochem. 1992 Dec;59(6):1987-96
references: 1431889
references: Neuron. 1997 Nov;19(5):1031-47
references: 9390517
references: Eur J Neurosci. 2002 Oct;16(8):1417-24
references: 12405954
references: Learn Mem. 2004 Mar-Apr;11(2):172-8
references: 15054132
references: Neuroreport. 2003 Aug 6;14(11):1481-3
references: 12960768
references: Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12068-72
references: 10518577
references: Cell. 2002 Mar 8;108(5):595-8
references: 11893331
references: Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15195-202
references: 8986787
references: Nature. 2005 Apr 14;434(7035):894-8
references: 15758952