Unilateral dialysis of the broad spectrum muscarinic receptor antagonist atropine (50 mM) into the ventral respiratory column (VRC; including the pre-Bӧtzinger 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 (NK-1) and 5-HT2A receptors does not alter V̇I or f, but increases local SP. Herein, we tested hypotheses that: 1) 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, 2) 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: 1) equivalent increases in local 5-HT and SP with 50 mM atropine dialysis during wakefulness compared to isoflurane anesthesia, but V̇I and f only increased while awake, 2) dialyses of the triple cocktail of antagonists increased V̇I, f, 5-HT, and SP (P < 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.
- pre-Bӧtzinger Complex
- ventral respiratory column
- Copyright © 2016, Journal of Applied Physiology