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State-dependent and -independent effects of dialyzing excitatory neuromodulator receptor antagonists into the ventral respiratory column. J Appl Physiol (1985) 2017 Feb 01;122(2):327-338



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2-s2.0-85014833742   3 Citations


Unilateral dialysis of the broad-spectrum muscarinic receptor antagonist atropine (50 mM) into the ventral respiratory column [(VRC) including the pre-Bötzinger complex region] of awake goats increased pulmonary ventilation (V̇i) and breathing frequency (f), conceivably due to local compensatory increases in serotonin (5-HT) and substance P (SP) measured in effluent mock cerebral spinal fluid (mCSF). In contrast, unilateral dialysis of a triple cocktail of antagonists to muscarinic (atropine; 5 mM), neurokinin-1, and 5-HT receptors does not alter V̇i or f, but increases local SP. Herein, we tested hypotheses that ) local compensatory 5-HT and SP responses to 50 mM atropine dialyzed into the VRC of goats will not differ between anesthetized and awake states; and ) bilateral dialysis of the triple cocktail of antagonists into the VRC of awake goats will not alter V̇i or f, but will increase local excitatory neuromodulators. Through microtubules implanted into the VRC of goats, probes were inserted to dialyze mCSF alone (time control), 50 mM atropine, or the triple cocktail of antagonists. We found ) equivalent increases in local 5-HT and SP with 50 mM atropine dialysis during wakefulness compared with isoflurane anesthesia, but V̇i and f only increased while awake; and ) dialyses of the triple cocktail of antagonists increased V̇i, f, 5-HT, and SP (<0.05) during both day and night studies. We conclude that the mechanisms governing local neuromodulator levels are state independent, and that bilateral excitatory receptor blockade elicits an increase in breathing, presumably due to a local, (over)compensatory neuromodulator response. The two major findings are as follows: 1) during unilateral dialysis of 50 mM atropine into the ventral respiratory column to block excitatory muscarinic receptor activity, a compensatory increase in other neuromodulators was state independent, but the ventilatory response appears to be state dependent; and 2) the hypothesis that absence of decreased V̇i and f during unilateral dialysis of excitatory receptor antagonists was due to compensation by the contralateral VRC was not supported by findings herein.

Author List

Langer TM 3rd, Neumueller SE, Crumley E, Burgraff NJ, Talwar S, Hodges MR, Pan L, Forster HV


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

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

Cerebrospinal Fluid
Muscarinic Antagonists
Neurotransmitter Agents
Pulmonary Ventilation
Receptors, Muscarinic
Receptors, Neurotransmitter
Receptors, Serotonin
Respiratory Center
Respiratory Mechanics
Substance P
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1