Reduction of voltage-dependent magnesium block of N-methyl-D-aspartate receptor-mediated current by in vivo axonal injury.
The post-traumatic change of the voltage-dependent Mg(2+) block of N-methyl-D-aspartate response was investigated using nystatin perforated patch recording mode under the voltage-clamp condition. Motor neurons of the dorsal motor nucleus of vagus nerve were freshly dissociated from rat brain at 2h to 10 days after receiving axonal crush injuries in vivo at the neck. The reduction of voltage-dependent Mg(2+) block of N-methyl-D-aspartate response became evident at more than 12h after the injury, sustained for at least five days and recovered within 10 days. Other characteristics examined such as reversal potentials, the Hill coefficient and EC(50) of N-methyl-D-aspartate-induced current were not affected by axonal injury. The Mg(2+) block of N-methyl-D-aspartate response was not affected at all by local application of colchicine onto the vagal axon in in vivo condition, suggesting that axonal injury, but not the blockade of the axonal flow, is responsible for the change of the sensitivity of N-methyl-D-aspartate response to extracellular Mg(2+). In addition, the reduction of Mg(2+) block by the nerve injury persisted regardless of the presence of protein kinase C modulators, such as 10(-6)M chelerythrine and 10(-7)M calphostin C. Therefore alteration of protein kinase C activity after axonal injury is not responsible for the maintenance of the reduced Mg(2+) block. These findings suggest that injured neurons acquire immature characteristics of plasticity with respect to the sensitivity of N-methyl-D-aspartate receptors to extracellular Mg(2+) or a long-term increase in the susceptibility to Ca(2+) excitotoxicity.
Furukawa
Y
Y
Department of Cellular and System Physiology, Graduate School of Medical Science, Kyushu University, 812-8582, Fukuoka, Japan.
Okada
M
M
Akaike
N
N
Hayashi
T
T
Nabekura
J
J
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D003078:Colchicine / Q000494:pharmacology; D006074:Gout Suppressants / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism* / Q000494:pharmacology*; D009409:Nerve Crush / Q000009:adverse effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology
D006074:Gout Suppressants; D016194:Receptors, N-Methyl-D-Aspartate; D008274:Magnesium; D003078:Colchicine