Neurotransmitters and neuromodulators controlling the hypoxic respiratory response in anaesthetized cats
Authors' present addresses P. M. Lalley: Department of Physiology, University of Wisconsin Medical Science Center, Madison, WI, USA.
O. Pierrefiche: Laboratoire de Physiologie Animale, Faculté des Sciences d'Amiens, France.
Corresponding author D. W. Richter: II. Physiologisches Institut, Universität Göttingen, Humboldtallee 23, 37073 Göttingen, Germany. Email: firstname.lastname@example.org
- 1The contributions of neurotransmitters and neuromodulators to the responses of the respiratory network to acute hypoxia were analysed in anaesthetized cats.
- 2Samples of extracellular fluid were collected at 1–1.5 min time intervals by microdialysis in the medullary region of ventral respiratory group neurones and analysed for their content of glutamate, γ-aminobutyric acid (GABA), serotonin and adenosine by high performance liquid chromatography. Phrenic nerve activity was correlated with these measurements.
- 3Levels of glutamate and GABA increased transiently during early periods of hypoxia, coinciding with augmented phrenic nerve activity and then fell below control during central apnoea. Serotonin and adenosine increased slowly and steadily with onset of hypoxic depression of phrenic nerve activity.
- 4The possibility that serotonin contributes to hypoxic respiratory depression was tested by microinjecting the 5-HT-1A receptor agonist 8-OH-DPAT into the medullary region that is important for rhythmogenesis. Hypoxic activation of respiratory neurones and phrenic nerve activity were suppressed. Microinjections of NAN-190, a 5-HT-1A receptor blocker, enhanced hypoxic augmentation resulting in apneustic prolongation of inspiratory bursts.
- 5The results reveal a temporal sequence in the release of neurotransmitters and neuromodulators and suggest a specific role for each of them in the sequential development of hypoxic respiratory disturbances.