High- and low-affinity NMDA receptor-binding sites in rat spinal cord: effects of traumatic injury

Abstract

N-methyl- d-aspartate (NMDA) receptor-mediated events have been implicated in the pathophysiology of posttraumatic spinal cord injury. In the present study, [ 3H]MK801 was used to analyse the changes in NMDA receptor-binding sites in rat spinal cord after impact trauma at T9. In contrast to brain, which showed only a single binding site, spinal cord showed both high-affinity ( K d1 = 0.47 ± 0.24nM ) and low-affinity ( K d2 = 7.75 ± 1.82nM ) binding sites with relatively low binding density ( B max1 = 0.11 ± 0.04pmol/mg protein and B max2 = 0.84 ± 0.11pmol/mg protein ). Time-course studies demonstrated significant decreases in the binding of [ 3H]MK801 at the thoracic and lumbar segments at 4 h after spinal cord injury with recovery by 24 h. Scatchard analyses indicate that these changes likely involve both high- and low-affinity binding sites. The transitory reduction in [ 3H]MK801-binding after trauma may reflect downregulationn of NMDA receptors as a consequence of posttraumatic glutamate release and may serve to limit excitotoxin-induced injury.