Neurokinin-1 receptor activation in Bötzinger complex evokes bradypnoea

Angelina Y. Fong, Jeffrey T. Potts*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    In the present study, we examined the role of the neurokinin-1 receptor (NK1R) in the modulation of respiratory rhythm in a functionally identified bradypnoeic region of the ventral respiratory group (VRG) in the in situ arterially perfused juvenile rat preparation. In electrophysiologically and functionally identified bradypnoeic sites corresponding to the Bötzinger complex (BötC), microinjection of the selective NK1R agonist [Sar9-Met(O2) 11]-substance P (SSP) produced a significant reduction in phrenic frequency mediated exclusively by an increase in expiratory duration (TE). The reduction was characterized by a significant increase in postinspiratory (post-I) duration with no effect on either late-expiratory duration (E2) or inspiratory duration (TI). In contrast, in a functionally identified tachypnoeic region, corresponding to the preBötzinger complex (Pre-BötC), control microinjection of SSP elicited tachypnoea. Pretreatment with the NK1R antagonist CP99994 in the BötC significantly attenuated the bradypnoeic response to SSP injection and blunted the increase in TE duration. This effect of SSP mimicked the extension of TE produced by activation of the Hering-Breuer reflex. Therefore, we hypothesized that activation of NK1Rs in the BötC is requisite for the expiratory-lengthening effect of the Hering-Breuer reflex. Unilateral electrical stimulation of the cervical vagus nerve produced bradypnoea by exclusively extending TE. Ipsilateral blockade of NK1Rs by CP99994 following blockade of the contralateral BötC by the GABAA receptor agonist muscimol significantly reduced the extension of TE produced by vagal stimulation. Results from the present study demonstrate that selective activation of NK1Rs in a functionally identified bradypnoeic region of the VRG can depress respiratory frequency by selectively lengthening post-I duration and provide evidence that endogenous activation of NK1Rs in the BötC appears to be involved in the expiratory-lengthening effect of the Hering-Breuer reflex. In conclusion, our findings demonstrate that selective activation of NK1Rs in discrete regions of the VRG can exert functionally diverse effects on breathing.

    Original languageEnglish
    Pages (from-to)869-885
    Number of pages17
    JournalJournal of Physiology
    Volume575
    Issue number3
    DOIs
    Publication statusPublished - Sep 2006

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