title: Pre-Bötzinger complex functions as a central hypoxia chemosensor for respiration in vivo.
abstract: Recently, we identified a region located in the pre-Bötzinger complex (pre-BötC; the proposed locus of respiratory rhythm generation) in which activation of ionotropic excitatory amino acid receptors using DL-homocysteic acid (DLH) elicits a variety of excitatory responses in the phrenic neurogram, ranging from tonic firing to a rapid series of high-amplitude, rapid rate of rise, short-duration inspiratory bursts that are indistinguishable from gasps produced by severe systemic hypoxia. Therefore we hypothesized that this unique region is chemosensitive to hypoxia. To test this hypothesis, we examined the response to unilateral microinjection of sodium cyanide (NaCN) into the pre-BötC in chloralose- or chloralose/urethan-anesthetized vagotomized, paralyzed, mechanically ventilated cats. In all experiments, sites in the pre-BötC were functionally identified using DLH (10 mM, 21 nl) as we have previously described. All sites were histologically confirmed to be in the pre-BötC after completion of the experiment. Unilateral microinjection of NaCN (1 mM, 21 nl) into the pre-BötC produced excitation of phrenic nerve discharge in 49 of the 81 sites examined. This augmentation of inspiratory output exhibited one of the following changes in cycle timing and/or pattern: 1) a series of high-amplitude, short-duration bursts in the phrenic neurogram (a discharge similar to a gasp), 2) a tonic excitation of phrenic neurogram output, 3) augmented bursts in the phrenic neurogram (i.e., eupneic breath ending with a gasplike burst), or 4) an increase in frequency of phrenic bursts accompanied by small increases or decreases in the amplitude of integrated phrenic nerve discharge. Our findings identify a locus in the brain stem in which focal hypoxia augments respiratory output. We propose that the respiratory rhythm generator in the pre-BötC has intrinsic hypoxic chemosensitivity that may play a role in hypoxia-induced gasping.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903-0019, USA.
authors.forename: I C
authors.initials: IC
authors.lastname: Solomon
authors.forename: N H
authors.initials: NH
authors.lastname: Edelman
authors.forename: J A
authors.initials: JA
authors.lastname: Neubauer
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000503:physiopathology; D002415:Cats; D002628:Chemoreceptor Cells / Q000378:metabolism*; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D010507:Periodicity; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D012121:Respiration, Artificial; D012125:Respiratory Center / Q000502:physiology*; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D012966:Sodium Cyanide / Q000008:administration & dosage; D014628:Vagotomy
chemical_list: D006710:Homocysteine; C007956:homocysteic acid; D012966:Sodium Cyanide