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The murine neurokinin NK 1 receptor gene contributes to the adult hypoxic facilitation of ventilation
Author(s) -
Ptak Krzysztof,
Burnet Henri,
Blanchi Bruno,
Sieweke Michael,
De Felipe Carmen,
Hunt Stephen P.,
Monteau Roger,
Hilaire Gérard
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02305.x
Subject(s) - respiratory system , receptor , neurokinin a , ventilation (architecture) , hypoxia (environmental) , control of respiration , biology , respiratory center , tachykinin receptor 1 , substance p , respiratory rate , endocrinology , medicine , chemistry , neuropeptide , mechanical engineering , organic chemistry , oxygen , engineering , heart rate , blood pressure
Substance P and neurokinin‐1 receptors (NK 1 ) modulate the respiratory activity and are expressed early during development. We tested the hypothesis that NK 1 receptors are involved in prenatal development of the respiratory network by comparing the resting respiratory activity and the respiratory response to hypoxia of control mice and mutant mice lacking the NK 1 receptor (NK 1 −/− ). In vitro and in vivo experiments were conducted on neonatal, young and adult mice from wild‐type and NK 1 −/− strains. In the wild strain, immunohistological, pharmacological and electrophysiological studies showed that NK 1 receptors were expressed within medullary respiratory areas prior to birth and that their activation at birth modulated central respiratory activity and the membrane properties of phrenic motoneurons. Both the membrane properties of phrenic motoneurons and the respiratory activity generated in vitro by brainstem‐spinal cord preparation from NK 1 −/− neonate mice were similar to that from the wild strain. In addition, in vivo ventilation recordings by plethysmography did not reveal interstrain differences in resting breathing parameters. The facilitation of ventilation by short‐lasting hypoxia was similar in wild and NK 1 −/− neonates but was significantly weaker in adult NK 1 −/− mice. Results demonstrate that NK 1 receptors do appear to be necessary for a normal respiratory response to short‐lasting hypoxia in the adult. However, NK 1 receptors are not obligatory for the prenatal development of the respiratory network, for the production of the rhythm, or for the regulation of breathing by short‐lasting hypoxia in neonates.