Contribution of the respiratory network to rhythm and motor output revealed by modulation of GIRK channels, somatostatin and neurokinin-1 receptors.
Breathing is generated by a respiratory network in the brainstem. At its core, a population of neurons expressing neurokinin-1 receptors (NK1R) and the peptide somatostatin (SST) form the preBötzinger Complex (preBötC), a site essential for the generation of breathing. PreBötC interneurons generate rhythm and follower neurons shape motor outputs by activating upper airway respiratory muscles. Since NK1R-expressing preBötC neurons are preferentially inhibited by μ-opioid receptors via activation of GIRK channels, NK1R stimulation may also involve GIRK channels. Hence, we identify the contribution of GIRK channels to rhythm, motor output and respiratory modulation by NK1Rs and SST. In adult rats, GIRK channels were identified in NK1R-expressing preBötC cells. Their activation decreased breathing rate and genioglossus muscle activity, an important upper airway muscle. NK1R activation increased rhythmic breathing and genioglossus muscle activity in wild-type mice, but not in mice lacking GIRK2 subunits (GIRK2(-/-)). Conversely, SST decreased rhythmic breathing via SST2 receptors, reduced genioglossus muscle activity likely through SST4 receptors, but did not involve GIRK channels. In summary, NK1R stimulation of rhythm and motor output involved GIRK channels, whereas SST inhibited rhythm and motor output via two SST receptor subtypes, therefore revealing separate circuits mediating rhythm and motor output.
Departments of Medicine and Physiology, University of Toronto, Toronto, Canada.
Gaspard
G
Montandon
Departments of Medicine and Physiology, University of Toronto, Toronto, Canada.
Hattie
H
Liu
Departments of Medicine and Physiology, University of Toronto, Toronto, Canada.
Richard L
RL
Horner
D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D012119:Respiration; D013004:Somatostatin / Q000502:physiology*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018040:Receptors, Neurokinin-1; D013004:Somatostatin