Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe area of awake goats. J Appl Physiol (1985) 2004 Dec;97(6):2236-47
Date
08/24/2004Pubmed ID
15322066DOI
10.1152/japplphysiol.00584.2004Scopus ID
2-s2.0-9244237596 (requires institutional sign-in at Scopus site) 45 CitationsAbstract
The major objective of this study was to gain insight into whether under physiological conditions medullary raphe area neurons influence breathing through CO(2)/H(+) chemoreceptors and/or through a postulated, nonchemoreceptor modulatory influence. Microtubules were chronically implanted into the raphe of adult goats (n = 13), and breathing at rest (awake and asleep), breathing during exercise, as well as CO(2) sensitivity were assessed repeatedly before and after sequential injections of the neurotoxins saporin conjugated to substance P [SP-SAP; neurokinin-1 receptor (NK1R) specific] and ibotenic acid (IA; nonspecific glutamate receptor excitotoxin). In all goats, microtubule implantation alone resulted in altered breathing periods, manifested as central or obstructive apneas, and fractionated breathing. The frequency and characteristics of the altered breathing periods were not subsequently affected by injections of the neurotoxins (P > 0.05). Three to seven days after SP-SAP or subsequent IA injection, CO(2) sensitivity was reduced (P < 0.05) by 23.8 and 26.8%, respectively, but CO(2) sensitivity returned to preinjection control values >7 days postinjection. However, there was no hypoventilation at rest (awake, non-rapid eye movement sleep, or rapid eye movement sleep) or during exercise after these injections (P > 0.05). The neurotoxin injections resulted in neuronal death greater than three times that with microtubule implantation alone and reduced (P < 0.05) both tryptophan hydroxylase-expressing (36%) and NK1R-expressing (35%) neurons at the site of injection. We conclude that both NK1R- and glutamate receptor-expressing neurons in the medullary raphe nuclei influence CO(2) sensitivity apparently through CO(2)/H-expressing chemoreception, but the altered breathing periods appear unrelated to CO(2) chemoreception and thus are likely due to non-chemoreceptor-related neuromodulation of ventilatory control mechanisms.
Author List
Hodges MR, Opansky C, Qian B, Davis S, Bonis J, Bastasic J, Leekley T, Pan LG, Forster HVAuthors
Hubert V. Forster PhD Professor in the Physiology department at Medical College of WisconsinMatthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCarbon Dioxide
Cell Count
Chemoreceptor Cells
Denervation
Excitatory Amino Acid Agonists
Female
Goats
Ibotenic Acid
Immunotoxins
Medulla Oblongata
Raphe Nuclei
Respiratory Mechanics
Ribosome Inactivating Proteins, Type 1
Substance P
Wakefulness