GABA, not glycine, mediates inhibition of latent respiratory motor pathways after spinal cord injury.
Previous work has shown that latent respiratory motor pathways known as crossed phrenic pathways are inhibited via a spinal inhibitory process; however, the underlying mechanisms remain unknown. The present study investigated whether spinal GABA-A and/or glycine receptors are involved in the inhibition of the crossed phrenic pathways after a C2 spinal cord hemisection injury. Under ketamine/xylazine anesthesia, adult, female, Sprague-Dawley rats were hemisected at the C2 spinal cord level. Following 1 week post injury, rats were anesthetized with urethane, vagotomized, paralyzed and ventilated. GABA-A receptor (bicuculline and Gabazine) and glycine receptor (strychnine) antagonists were applied directly to the cervical spinal cord (C3-C7), while bilateral phrenic nerve motor output was recorded. GABA-A receptor antagonists significantly increased peak phrenic amplitude bilaterally and induced crossed phrenic activity in spinal-injured rats. Muscimol, a specific GABA-A receptor agonist, blocked these effects. Glycine receptor antagonists applied directly to the spinal cord had no significant effect on phrenic motor output. These results indicate that phrenic motor neurons are inhibited via a GABA-A mediated receptor mechanism located within the spinal cord to inhibit the expression of crossed phrenic pathways.
Zimmer
M Beth
MB
Department of Anatomy and Cell Biology, Wayne State University, 540 East Canfield, Detroit, MI 48201, USA. mzimmer@med.wayne.edu
Goshgarian
Harry G
HG
D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D004525:Efferent Pathways / Q000166:cytology / Q000503:physiopathology*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000502:physiology*; D018684:Glycine Agents / Q000494:pharmacology; D010791:Phrenic Nerve / Q000473:pathology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors; D015656:Respiratory Mechanics / Q000502:physiology*; D012132:Respiratory Muscles / Q000294:innervation* / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013238:Stereotaxic Techniques; D013331:Strychnine / Q000494:pharmacology; D014628:Vagotomy; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D018684:Glycine Agents; D011724:Pyridazines; D018009:Receptors, Glycine; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; C049853:gabazine; D013331:Strychnine; D005998:Glycine; D001640:Bicuculline