Evidence for respiratory neuromodulator interdependence after cholinergic disruption in the ventral respiratory column

Respir Physiol Neurobiol. 2015 Jan 1:205:7-15. doi: 10.1016/j.resp.2014.09.010. Epub 2014 Sep 26.

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.

Keywords: Control of breathing; Muscarinic receptor; Neuromodulator interdependence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Atropine / administration & dosage
  • Chromatography, High Pressure Liquid
  • Goats
  • Microdialysis
  • Muscarinic Antagonists / administration & dosage*
  • Neurotransmitter Agents / metabolism*
  • Receptors, Muscarinic / metabolism
  • Respiration / drug effects
  • Respiratory Center / drug effects
  • Respiratory Center / physiology*
  • Respiratory Physiological Phenomena*

Substances

  • Muscarinic Antagonists
  • Neurotransmitter Agents
  • Receptors, Muscarinic
  • Atropine