title: Inhibitory input from slowly adapting lung stretch receptors to retrotrapezoid nucleus chemoreceptors.
abstract: The retrotrapezoid nucleus (RTN) contains CO(2)-activated interneurons with properties consistent with central respiratory chemoreceptors. These neurons are glutamatergic and express the transcription factor Phox2b. Here we tested whether RTN neurons receive an input from slowly adapting pulmonary stretch receptors (SARs) in halothane-anaesthetized ventilated rats. In vagotomized rats, RTN neurons were inhibited to a variable extent by stimulating myelinated vagal afferents using the lowest intensity needed to inhibit the phrenic nerve discharge (PND). In rats with intact vagus nerves, RTN neurons were inhibited, also to a variable extent, by increasing positive end-expiratory pressure (PEEP; 2-6 cmH(2)O). The cells most sensitive to PEEP were inhibited during each lung inflation at rest and were instantly activated by stopping ventilation. Muscimol (GABA-A agonist) injection in or next to the solitary tract at area postrema level desynchronized PND from ventilation, eliminated the lung inflation-synchronous inhibition of RTN neurons and their steady inhibition by PEEP but did not change their CO(2) sensitivity. Muscimol injection into the rostral ventral respiratory group eliminated PND but did not change RTN neuron response to either lung inflation, PEEP increases, vagal stimulation or CO(2). Generalized glutamate receptor blockade with intracerebroventricular (i.c.v.) kynurenate eliminated PND and the response of RTN neurons to lung inflation but did not change their CO(2) sensitivity. PEEP-sensitive RTN neurons expressed Phox2b. In conclusion, RTN chemoreceptors receive an inhibitory input from myelinated lung stretch receptors, presumably SARs. The lung input to RTN may be di-synaptic with inhibitory pump cells as sole interneurons.
authors.affiliation: Department of Pharmacology, University of Virginia Health System, PO Box 800735, 1300 Jefferson Park Avenue, Charlottesville, VA 22908-0735, USA.
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Moreira
authors.forename: Ana C
authors.initials: AC
authors.lastname: Takakura
authors.forename: Eduardo
authors.initials: E
authors.lastname: Colombari
authors.forename: Gavin H
authors.initials: GH
authors.lastname: West
authors.forename: Patrice G
authors.initials: PG
authors.lastname: Guyenet
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D002628:Chemoreceptor Cells / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D007276:Injections, Intraventricular; D007736:Kynurenic Acid / Q000494:pharmacology; D008168:Lung / Q000294:innervation / Q000502:physiology*; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology*; D008526:Medulla Oblongata / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D010791:Phrenic Nerve / Q000502:physiology; D010812:Physical Stimulation; D011175:Positive-Pressure Respiration; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000502:physiology; D017552:Solitary Nucleus / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014630:Vagus Nerve / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors; D002245:Carbon Dioxide; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D007736:Kynurenic Acid