Neurokinin-1 receptors modulate the excitability of expiratory neurons in the ventral respiratory group.
We studied the role of neurokinin-1 receptors (NK1-R) on the excitability of expiratory (E) neurons (tonic discharge, E(TONIC); augmenting, E(AUG); decrementing, E(DEC)) throughout the ventral respiratory group, including Bötzinger Complex (BötC) using extracellular single-unit recording combined with pressurized picoejection in decerebrate, arterially perfused juvenile rats. Responses evoked by picoejection of the NK1-R agonist, [Sar9-Met(O2)11]-substance P (SSP) were determined before and after the selective NK1-R antagonist, CP99,994. SSP excited 20 of 35 expiratory neurons by increasing the number of action potentials per burst (+33.7 +/- 6.5% of control), burst duration (+20.6 +/- 7.9% of control), and peak firing frequency (+16.2 +/- 4.8% of control; means +/- SE). Pretreatment with CP99,994 completely blocked SSP-evoked excitation in a subset of neurons tested, supporting the notion that SSP excitation was mediated through NK1-R activation. Because we had previously shown that E(AUG) neurons were crucial to locomotor-respiratory coupling (LRC), we reasoned that blockade of NK1-R would alter LRC by preventing somatic-evoked excitation of E(AUG) neurons. Blockade of NK1-Rs by CP99,994 in the BötC severely disrupted LRC and prevented somatic-evoked excitation of E(AUG) neurons. These findings demonstrate that LRC is dependent on endogenous SP release acting via NK1-Rs on E(AUG) neurons of the BötC. Taken together with our earlier finding that inspiratory off-switching by the Hering-Breuer Reflex requires endogenous activation of NK1-Rs through activation of NK1-Rs on E(DEC) neurons, we suggest that endogenous release of substance P in the BötC provides a reflex pathway-dependent mechanism to selectively modulate respiratory rhythm.
Dalton Cardiovascular Research Center , University of Missouri, Columbia, Missouri, USA.
Angelina Y
AY
Fong
Jeffrey T
JT
Potts
D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000502:physiology / Q000528:radiation effects; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D045853:Exhalation / Q000187:drug effects / Q000502:physiology*; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D012125:Respiratory Center / Q000166:cytology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D006710:Homocysteine; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C010982:homocysteinesulfinic acid; D013373:Substance P