The murine neurokinin NK₁ receptor gene contributes to the adult hypoxic facilitation of ventilation

Abstract

Substance P and neurokinin-1 receptors (NK1) modulate the respiratory activity and are expressed early during development. We tested the hypothesis that NK1 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 NK1 receptor (NK1-/-). In vitro and in vivo experiments were conducted on neonatal, young and adult mice from wild-type and NK1-/- strains. In the wild strain, immunohistological, pharmacological and electrophysiological studies showed that NK1 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 NK1-/- 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 NK1-/- neonates but was significantly weaker in adult NK1-/- mice. Results demonstrate that NK1 receptors do appear to be necessary for a normal respiratory response to short-lasting hypoxia in the adult. However, NK1 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.

Quantitative study of NPY‐expressing GABAergic neurons and axons in rat spinal dorsal horn

“…We have also shown that it stains identical structures to those detected by a rabbit antibody (Polgár et al, 1999b), which gives no immunostaining in central nervous system (CNS) tissue from NK1r −/− mice (Ptak et al, 2002). …”

De novo expression of neurokinin‐1 receptors by spinoparabrachial lamina I pyramidal neurons following a peripheral nerve lesion

“…In Western blots from rat brain, it recognizes a single band at 46 kDa, whose staining is specifically inhibited by incubation with the blocking peptide (data supplied by the manufacturer). Furthermore, it was shown that it does not produce any staining in NK-1r knockout mice, although it recognizes the receptor in wild-type mice (Ptak et al, 2002).…”

Neurokinin-1 Receptors Modulate the Excitability of Expiratory Neurons in the Ventral Respiratory Group

“…The role of SP and NK1-R has been the focus of much research as it is involved in mediating a number of respiratory reflex responses, including hypoxic ventilatory response and central chemosensitivity (Chen et al 1990a;Gray et al 2001;Mazzone et al 1997;Nattie and Li 2002;Ptak et al 2002;Wickstrom et al 2004). Although NK1-R are localized throughout the VRG (Gray et al 1999;Guyenet et al 2002;Nakaya et al 1994;Wang et al 2001) with expression confirmed on preinspiratory neurons , the effect of direct activation of NK1-R expressing expiratory neurons on respiratory rhythm has not been thoroughly explored.…”