Reorganisation of respiratory network activity after loss of glycinergic inhibition.
gamma-Aminobutyric acid (GABA)-ergic and glycinergic inhibition is believed to play a major role in the respiratory network. In the present study we tested whether specific blockade of glycinergic inhibition resulted in changes in respiratory network interaction and function. Using the working heart-brainstem preparation from adult mice, we recorded phrenic nerve activity and the activity of different types of respiratory neurones located in the ventrolateral medulla. Strychnine (0.03-0.3 microM) was given systemically to block glycine receptors (Gly-R). During exposure to strychnine, post-inspiratory (PI) neurones shifted their onset of discharge into the inspiratory phase. As a consequence, the post-inspiratory phase failed and the rhythm changed from a three-phase cycle (inspiration, post-inspiration, expiration, with a frequency of about. 0.24 Hz) to a faster, two-phased cycle (inspiration expiration, frequency about 0.41 Hz). Inspiratory and expiratory neurones altered their augmenting membrane potential pattern to a rapidly peaking pattern. Smaller voltage oscillations at approximately 10 Hz and consisting of excitatory and inhibitory postsynaptic potential sequences occurred during the expiratory interval. Due to their high frequency and low amplitude, such oscillations would be inadequate for lung ventilation. We conclude that, under physiological conditions, glycinergic inhibition does indeed play a major role in the generation of a normal respiratory rhythm in adult mice. After failure of glycinergic inhibition a faster respiratory rhythm seems to operate through reciprocal GABAergic inhibition between inspiratory and expiratory neurones, while phase switching is organised by activation of intrinsic membrane properties.
Büsselberg
D
D
Georg-August-Universität Göttingen, II Department of Physiology, Germany. Bberg@neuro-physiol.med.uni-goettingen.de
Bischoff
A M
AM
Paton
J F
JF
Richter
D W
DW
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000037:antagonists & inhibitors* / Q000502:physiology; D008526:Medulla Oblongata / Q000502:physiology; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology; D010721:Phosphinic Acids / Q000494:pharmacology; D010791:Phrenic Nerve / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors; D012119:Respiration; D012137:Respiratory System / Q000294:innervation*; D013331:Strychnine / Q000494:pharmacology
D018756:GABA Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D018079:Receptors, GABA; D018009:Receptors, Glycine; C085075:CGP 55845A; D013331:Strychnine; D005998:Glycine; D001640:Bicuculline