A role of GABAA receptors in hypoxia-induced conduction failure of neonatal rat spinal dorsal column axons.
GABA (gamma-aminobutyric acid) depresses axonal conduction in neonatal dorsal columns. GABA released by injured spinal neurons may diffuse to white matter and contribute to secondary axonal damage. We studied the effects of hypoxia and GABAA receptor blockade on dorsal column conduction in vitro. The experiments compared the effects of hypoxia on longitudinally hemisected spinal cords and isolated neonatal dorsal columns. Before hypoxia, electrical stimulation elicited robust conducted compound action potentials in both isolated dorsal columns and hemicords. The tissues were superfused for 120 min with a hypoxic Ringer's solution saturated with 95% N2 and 5% CO2, followed by oxygenated Ringer's solution for 90 min. Isolated dorsal columns were remarkably insensitive to hypoxia. Response amplitudes fell by only 11 +/- 7% (n = 5) during hypoxia. In hemicords, however, hypoxia reduced response amplitudes by 56 +/- 16% (n = 5, mean +/- S.E.M.) and re-oxygenation did not restore response amplitude. We applied bicucullin (10(-5) M) to block GABAA receptors in the hemicords during hypoxia. Response amplitudes in bicucullin-treated hemicords fell by only 3 +/- 9% (n = 5) during hypoxia but declined 31 +/- 5% during re-oxygenation. These results suggest that endogenous GABA released from gray matter contributes to hypoxia-induced dorsal-column conduction failure.
Department of Neurosurgery, New York University Medical Center, NY 10016.
M
M
Lee
K
K
Sakatani
W
W
Young
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001369:Axons / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D058787:GABA-A Receptor Antagonists; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D001640:Bicuculline