title: Evidence for respiratory neuromodulator interdependence after cholinergic disruption in the ventral respiratory column.
abstract: Reverse dialysis of the muscarinic receptor antagonist, atropine (ATR, 50 mM), into the pre-Bötzinger Complex region of the ventral respiratory column (VRC) of awake and sleeping goats increases breathing frequency and serotonin (5-HT), substance P (SP), glycine, and GABA concentrations in the effluent dialysate. Herein, we report data from goats in which we reverse dialyzed 5 mM ATR or specific antagonists of M2 or M3 muscarinic receptors into the VRC. The effects on frequency of all three antagonists were not significantly different from time control studies. 5 mM ATR and the M3 antagonist increased SP sevenfold less than 50 mM ATR. The antagonists had no effect on 5-HT, glycine, and/or GABA, suggesting that the increases in glycine and GABA with 50 mM ATR were secondary to the larger increases in 5-HT and/or SP. These data are suggestive of neuromodulator interdependence, whereby attenuation of one neuromodulator is compensated for by local changes in other neuromodulators to stabilize breathing.
authors.affiliation: Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: cmuere@mcw.edu.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Muere
authors.affiliation: Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: sneumueller@mcw.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Neumueller
authors.affiliation: Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: jumiller@mcw.edu.
authors.forename: Justin
authors.initials: J
authors.lastname: Miller
authors.affiliation: Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: solesiak@mcw.edu.
authors.forename: Samantha
authors.initials: S
authors.lastname: Olesiak
authors.affiliation: Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: mhodges@mcw.edu.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hodges
authors.affiliation: Physical Therapy, Marquette University, Milwaukee, WI 53201, USA. Electronic address: lawrence.pan@marquette.edu.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Pan
authors.affiliation: Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, USA. Electronic address: bforster@mcw.edu.
authors.forename: Hubert V
authors.initials: HV
authors.lastname: Forster
mesh_terms: D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D002851:Chromatography, High Pressure Liquid; D006041:Goats; D017551:Microdialysis; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D012125:Respiratory Center / Q000187:drug effects / Q000502:physiology*; D012143:Respiratory Physiological Phenomena
chemical_list: D018727:Muscarinic Antagonists; D018377:Neurotransmitter Agents; D011976:Receptors, Muscarinic; D001285:Atropine
keywords: Control of breathing; Muscarinic receptor; Neuromodulator interdependence