Faculty Collaboration Database

Combined unilateral blockade of cholinergic, peptidergic, and serotonergic receptors in the ventral respiratory column does not affect breathing in awake or sleeping goats. J Appl Physiol (1985) 2015 Aug 01;119(3):308-20

Date

05/30/2015

Pubmed ID

26023224

Pubmed Central ID

PMC4526704

DOI

10.1152/japplphysiol.00145.2015

Scopus ID

2-s2.0-84939865619 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Previous work in intact awake and sleeping goats has found that unilateral blockade of excitatory inputs in the ventral respiratory column (VRC) elicits changes in the concentrations of multiple neurochemicals, including serotonin (5-HT), substance P, glycine, and GABA, while increasing or having no effect on breathing. These findings are consistent with the concept of interdependence between neuromodulators, whereby attenuation of one modulator elicits compensatory changes in other modulators to maintain breathing. Because there is a large degree of redundancy and multiplicity of excitatory inputs to the VRC, we herein tested the hypothesis that combined unilateral blockade of muscarinic acetylcholine (mACh), neurokinin-1 (NK1, the receptor for substance P), and 5-HT2A receptors would elicit changes in multiple neurochemicals, but would not change breathing. We unilaterally reverse-dialyzed a cocktail of antagonists targeting these receptors into the VRC of intact adult goats. Breathing was continuously monitored while effluent fluid from dialysis was collected for quantification of neurochemicals. We found that neither double blockade of mACh and NK1 receptors, nor triple blockade of mACh, NK1, and 5-HT2A receptors significantly affected breathing (P ≥ 0.05) in goats that were awake or in non-rapid eye movement (NREM) sleep. However, both double and triple blockade increased the effluent concentration of substance P (P < 0.001) and decreased GABA concentrations. These findings support our hypothesis and, together with past data, suggest that both in wakefulness and NREM sleep, multiple neuromodulator systems collaborate to stabilize breathing when a deficit in one or multiple excitatory neuromodulators exists.

Author List

Muere C, Neumueller S, Olesiak S, Miller J, Langer T, Hodges MR, Pan L, Forster HV

Authors

Hubert V. Forster PhD Professor in the Physiology department at Medical College of Wisconsin
Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cholinergic Antagonists
Female
Goats
Lung
Neurotransmitter Agents
Receptors, Cholinergic
Receptors, Neuropeptide
Receptors, Neurotransmitter
Receptors, Serotonin
Respiratory Center
Respiratory Mechanics
Serotonin Antagonists
Sleep
Wakefulness