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This Article Full Text Full Text (PDF) All Versions of this Article: 575/3/869    most recent jphysiol.2006.114314v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fong, A. Y. Articles by Potts, J. T. Search for Related Content PubMed PubMed Citation Articles by Fong, A. Y. Articles by Potts, J. T. Related Collections Respiratory

¹ Dalton Cardiovascular Research Center
² Department of Veterinary Biomedical Science, University of Missouri, Columbia, MO, USA

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 (T_E). 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 (T_I). 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 T_E duration. This effect of SSP mimicked the extension of T_E 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 T_E. Ipsilateral blockade of NK1Rs by CP99994 following blockade of the contralateral BötC by the GABA_A receptor agonist muscimol significantly reduced the extension of T_E 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.

(Received 26 May 2006; accepted after revision 30 June 2006; first published online 6 July 2006)
Corresponding author J. T. Potts: Department of Biomedical Science, College of Veterinary Medicine, Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Dr., Columbia, MO 65211, USA. Email: pottsjt{at}missouri.edu

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