Hypoxic failure of synaptic transmission in the isolated spinal cord, and the effects of divalent cations.
Responses evoked by stimulation of a dorsal root were recorded from ventral and dorsal roots of isolated spinal cords of infant mice. Interstitial potassium, [K+]o, and extracellular DC voltage were recorded from dorsal gray matter in some experiments. When oxygen was withdrawn, synaptically transmitted discharges (dorsal horn response, DHR, and monosynaptic ventral root reflex, VRR) began to be depressed within a minute, and were depressed to less than 30% of control amplitude in 10-15 min. Responses recovered fully if oxygen was readmitted within 45 min, but no recovery was seen after 90 min of hypoxia. The degree of the depression of VRR was as expected from the depression of the electrotonically conducted excitatory postsynaptic potential (VRepsp). Responses failed much more rapidly in spinal cords of 15-16-day-old mice, than of 9-14-day-olds. When the spinal cord was bathed in elevated [Ca2+]o or in reduced [Mg2+]o, synaptic transmission was consistently maintained for a longer period of hypoxia than in bathing fluid of normal cation content. In a sizeable minority of the trials during hypoxia an abrupt increase of [K+]o occurred, accompanied by a sudden negative shift of extracellular potential, closely resembling spreading depression (SD) of forebrain structures. Delayed post-hypoxic spontaneous activity was seen in many spinal cords. The results are compatible with the hypothesis that hypoxic failure of synaptic transmission is due, in part or whole, to blockade of inward Ca2(+)-current in presynaptic terminals. Cells in spinal gray matter can no longer be regarded as 'immune' to SD-like depolarization, but the limited conditions under which SD can occur are not yet clear.
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Division of Physiology, Duke University Medical Center, Durham, NC 27710.
Somjen
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D000375:Aging; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent; D004558:Electric Stimulation; D005071:Evoked Potentials; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology*; D051379:Mice; D011188:Potassium / Q000494:pharmacology; D012018:Reflex; D013116:Spinal Cord / Q000254:growth & development / Q000502:physiology* / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D002413:Cations, Divalent; D008274:Magnesium; D011188:Potassium; D002118:Calcium