title: Activation of alpha-2 noradrenergic receptors is critical for the generation of fictive eupnea and fictive gasping inspiratory activities in mammals in vitro.
abstract: Biogenic amines are not just 'modulators', they are often essential for the execution of behaviors. Here, we explored the role of biogenic amines acting on the pre-Bötzinger complex (pre-BötC), an area located in the ventrolateral medulla which is critical for the generation of different forms of breathing. Isolated in transverse slices from mice, this region continues to spontaneously generate rhythmic activities that resemble normal (eupneic) inspiratory activity in normoxia and gasping in hypoxia. We refer to these as 'fictive eupneic' and 'fictive gasping' activity. When exposed to hypoxia, the pre-BötC transitions from a network state relying on calcium-activated nonspecific cation currents (I(CAN)) and persistent sodium currents (I(Nap)) to one that primarily depends on the I(Nap) current. Here we show that in inspiratory neurons I(Nap)-dependent bursting, blocked by riluzole, but not I(CAN) -dependent bursting, required endogenously released norepinephrine acting on alpha2-noradrenergic receptors (α2-NR). At the network level, fictive eupneic activity persisted while fictive gasping ceased following the blockade of α2-NR. Blockade of α2-NR eliminated fictive gasping even in slice preparations as well as in inspiratory island preparations. Blockade of fictive gasping by α2-NR antagonists was prevented by activation of 5-hydroxytryptamine type 2A receptors (5-HT2A). Our data suggest that gasping depends on the converging aminergic activation of 5-HT2AR and α2-NR acting on riluzole-sensitive mechanisms that have been shown to be crucial for gasping.
authors: Laboratoire Plasticité et Physio-Pathologie de la motricité, CNRS UMR 6196, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France. viemari@dpm.cnrs-mrs.fr
authors: Jean-Charles
authors: JC
authors: Viemari
authors: Alfredo J
authors: AJ
authors: Garcia
authors: Atsushi
authors: A
authors: Doi
authors: Jan-Marino
authors: JM
authors: Ramirez
references: Pediatrics. 1998 Feb;101(2):285-8
references: 9445505
references: Pediatr Res. 2004 Sep;56(3):391-5
references: 15240857
references: J Neurophysiol. 1998 Jun;79(6):2911-8
references: 9636097
references: Respir Physiol. 1969 Oct;7(3):356-68
references: 5387857
references: J Neurophysiol. 1999 Nov;82(5):2163-70
references: 10561396
references: Early Hum Dev. 2008 Apr;84(4):225-9
references: 17614220
references: J Neurophysiol. 2006 Mar;95(3):1334-44
references: 16492945
references: J Neurosci. 2003 Apr 15;23(8):3538-46
references: 12716963
references: Nat Neurosci. 2008 May;11(5):538-40
references: 18391943
references: Brain Res. 1979 Jan 5;160(1):57-68
references: 758223
references: J Neurosci. 1996 Aug 1;16(15):4596-603
references: 8764648
references: Pediatr Pulmonol. 2003 Aug;36(2):113-22
references: 12833490
references: Pediatr Pulmonol. 2008 Nov;43(11):1045-1060
references: 18831533
references: J Appl Physiol (1985). 2007 Jul;103(1):220-7
references: 17412795
references: Respir Physiol Neurobiol. 2009 Aug 31;168(1-2):69-75
references: 19538922
references: J Neurophysiol. 2006 Apr;95(4):2070-82
references: 16394066
references: J Neurosci. 2010 Jun 16;30(24):8251-62
references: 20554877
references: J Neurophysiol. 2002 Jun;87(6):2964-71
references: 12037199
references: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11742-6
references: 19553211
references: Biol Neonate. 1994;65(3-4):194-7
references: 8038282
references: Respir Physiol Neurobiol. 2003 Dec 16;139(1):113-9
references: 14637318
references: J Physiol. 2008 May 1;586(9):2245-6
references: 18450782
references: J Neurophysiol. 2002 Jul;88(1):206-13
references: 12091546
references: Respir Physiol Neurobiol. 2005 Nov 15;149(1-3):243-55
references: 15941675
references: Clin Exp Pharmacol Physiol. 2009 Dec;36(12):1218-28
references: 19793109
references: Prog Brain Res. 1991;88:365-80
references: 1813926
references: J Neurosci. 2005 Jan 12;25(2):446-53
references: 15647488
references: J Appl Physiol (1985). 1993 Jun;74(6):2801-11
references: 8365984
references: J Appl Physiol (1985). 2009 Jun;106(6):1785-92
references: 19213929
references: Pflugers Arch. 2001 Jan;441(4):444-9
references: 11212206
references: J Appl Physiol (1985). 2008 Mar;104(3):665-73
references: 18162482
references: J Physiol Paris. 2006 Nov-Dec;100(5-6):271-83
references: 17689057
references: J Appl Physiol (1985). 2008 May;104(5):1522-30
references: 18218910
references: Hum Mol Genet. 2003 Dec 1;12(23):3173-80
references: 14532329
references: J Neurophysiol. 2008 May;99(5):2114-25
references: 18287547
references: J Appl Physiol (1985). 2008 Jun;104(6):1828-34
references: 18420716
references: J Neurophysiol. 2001 Jul;86(1):104-12
references: 11431492
references: Early Hum Dev. 2003 Dec;75 Suppl:S129-38
references: 14693399
references: Biochemistry. 1997 May 27;36(21):6415-23
references: 9174358
references: J Neurosci. 1998 Dec 15;18(24):10652-62
references: 9852600
references: J Physiol. 2007 Jul 1;582(Pt 1):113-25
references: 17446214
references: Respir Physiol. 2001 Dec;129(1-2):191-209
references: 11738654
references: J Neurophysiol. 2001 Apr;85(4):1772-6
references: 11287498
references: J Chem Neuroanat. 2009 May;37(3):149-57
references: 19152834
references: J Neurosci. 2008 Nov 12;28(46):11806-13
references: 19005044
references: Neuron. 2004 Jul 8;43(1):105-17
references: 15233921
references: J Neurophysiol. 2006 Mar;95(3):1323-33
references: 16492944
references: Respir Physiol. 1997 Nov;110(2-3):71-85
references: 9407602
references: Neuroscience. 2011 Feb 23;175:262-72
references: 21130842
references: J Neurosci. 2006 Mar 8;26(10):2623-34
references: 16525041
references: Nat Neurosci. 2000 Jun;3(6):600-7
references: 10816317
references: J Neurosci. 2004 Jan 28;24(4):928-37
references: 14749437
references: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2939-44
references: 19196976
references: Mol Pharmacol. 1996 Aug;50(2):407-14
references: 8700150
references: J Neurophysiol. 1995 Apr;73(4):1452-61
references: 7643160
references: JAMA. 2010 Feb 3;303(5):430-7
references: 20124538
references: Nat Neurosci. 2006 Mar;9(3):311-3
references: 16474390
references: Pediatr Dev Pathol. 2005 Sep-Oct;8(5):507-24
references: 16222475
references: Curr Opin Neurobiol. 2004 Dec;14(6):665-74
references: 15582367
references: J Neurophysiol. 1997 Apr;77(4):1853-60
references: 9114241
references: J Neurophysiol. 2009 Feb;101(2):737-49
references: 19019973
references: Science. 1991 Nov 1;254(5032):726-9
references: 1683005
references: J Physiol. 1996 Mar 15;491 ( Pt 3):799-812
references: 8815212
references: Respir Physiol Neurobiol. 2006 Sep 28;153(2):126-38
references: 16309976
references: J Neurosci. 2002 Dec 15;22(24):11055-64
references: 12486201
references: J Appl Physiol (1985). 1989 May;66(5):2384-90
references: 2745303
references: Pediatr Res. 1999 Mar;45(3):350-4
references: 10088653
references: J Comp Neurol. 1997 Nov 17;388(2):169-90
references: 9368836
references: Neurosci Lett. 2007 Mar 30;415(3):288-93
references: 17276002
references: J Appl Physiol (1985). 2009 Sep;107(3):679-85
references: 19213935
references: Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):96-104
references: 18602029
references: Nat Rev Neurosci. 2006 Mar;7(3):232-42
references: 16495944
references: Respir Physiol Neurobiol. 2008 Dec 10;164(1-2):123-30
references: 18634907
references: J Neurophysiol. 2011 Feb;105(2):625-39
references: 21084689
references: Trends Pharmacol Sci. 1999 Jul;20(7):268-70
references: 10390643
references: Neurochem Int. 2006 Dec;49(7):698-707
references: 16962210
references: J Neurosci. 2008 Mar 5;28(10):2447-58
references: 18322090