P2Y₁Receptor Modulation of the Pre-Bötzinger Complex Inspiratory Rhythm Generating NetworkIn Vitro

Abstract

ATP is released during hypoxia from the ventrolateral medulla (VLM) and activates purinergic P2 receptors (P2Rs) at unknown loci to offset the secondary hypoxic depression of breathing. In this study, we used rhythmically active medullary slices from neonatal rat to map, in relation to anatomical and molecular markers of the pre-Bötzinger complex (preBötC) (a proposed site of rhythm generation), the effects of ATP on respiratory rhythm and identify the P2R subtypes responsible for these actions. Unilateral microinjections of ATP in a three-dimensional grid within the VLM revealed a "hotspot" where ATP (

Identification of a Cholinergic Modulatory and Rhythmogenic Mechanism within the Lamprey Respiratory Network

“…In addition, the following antagonists of fast excitatory and inhibitory transmission were used: 100 M D-(Ϫ)-2-amino-5-phosphonopentanoic acid (D-AP5; an NMDA receptor antagonist; Tocris Bioscience), 20 -100 M 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; a nonNMDA receptor antagonist; Tocris Bioscience), 10 M bicuculline methiodide (a GABA A receptor antagonist; Sigma-Aldrich), and 10 M strychnine (a glycine receptor antagonist; Tocris Bioscience). The drug concentrations and the application time were similar to those used in previous studies (Bongianni et al, 1999(Bongianni et al, , 2002(Bongianni et al, , 2006Aberger et al, 2001;Le Ray et al, 2003Shao and Feldman, 2002;Tryba et al, 2003;Peña et al, 2004;Del Negro et al, 2005;Lorier et al, 2007;Shao et al, 2008;St. John and Leiter, 2008;Mutolo et al, 2010).…”

Mecanismos purinérgicos no bulbo ventrolateral rostral modulam respostas cardiovasculares e respiratórias promovidas pela ativação dos quimiorreceptores centrais e periféricos.

“…It was shown previously that P2Y1 receptors mediate the excitatory effects of ATP on neurons in the preBötzinger complex (Lorier et al 2007(Lorier et al , 2008. However, we found that P2Y1 receptors are not expressed by chemosensitive RTN neurons and do not contribute to CO 2 /H + sensitivity of these cells in vitro or to CO 2 -induced changes in breathing or blood pressure in vivo.…”

“…Não podemos descartar a participação de outros receptores P2Y, pois resultados recentes mostraram que os receptores P2Y são os receptores purinérgicos mais abundantes na região do Complexo de Pré-Botzinger e medeiam as respostas respiratórias produzidas pelo ATP (FUNK, 2013;LORIER et al, 2007LORIER et al, , 2008.…”

“…Of these, P2Y1 receptors have been shown to function as the primary substrate for ATP-mediated activation of inspiratory neurons in the preBötzinger complex (Lorier et al 2007(Lorier et al , 2008, a region critically involved in inspiratory rhythm generation (Smith et al 1991). Therefore, we considered the possibility that P2Y1 receptors also contribute to up-stream purinergic modulation of CO 2 /H + -sensitive RTN neurons.…”

“…n = 6 ratos. (GOURINE et al, 2005a; BAYLISS, 2015; MOREIRA et al, 2015;SOBRINHO et al, 2014; LOESCHCKE, 1979; LAZARENKO et al, 2011; TAKAKURA et al, 2008; (FUNK, 2013;LORIER et al, 2007LORIER et al, , 2008. …”