MacLean J N, Schmidt B J
Department of Physiology, University of Manitoba, 730 William Ave., Winnipeg, Manitoba R3E 3J7, Canada.
J Neurophysiol. 2001 Sep;86(3):1131-8. doi: 10.1152/jn.2001.86.3.1131.
Both N-methyl-D-aspartate (NMDA) and serotonin (5-HT) receptors contribute to the generation of rhythmic motor patterns in the rat spinal cord. Co-application of these chemicals is more effective at producing locomotor-like activity than either neurochemical alone. In addition, NMDA application to rat spinal motoneurons, synaptically isolated in tetrodotoxin, induces nonlinear membrane behavior that results in voltage oscillations which can be blocked by 5-HT antagonists. However, the mechanisms underlying NMDA and 5-HT receptor interactions pertinent to motor rhythm production remain to be determined. In the present study, an in vitro neonatal rat spinal cord preparation was used to examine whether NMDA receptor-mediated nonlinear membrane voltage is modulated by 5-HT. Whole-cell recordings of spinal motoneurons demonstrated that 5-HT shifts the region of NMDA receptor-dependent negative slope conductance (RNSC) of the current-voltage relationship to more hyperpolarized potentials and enhances whole-cell inward current. The influence of 5-HT on the RNSC was similar to the effect on the RNSC of decreasing the extracellular Mg(2+)concentration. The results suggest that 5-HT may modulate this form of membrane voltage nonlinearity by regulating Mg(2+) blockade of the NMDA ionophore.
N-甲基-D-天冬氨酸(NMDA)受体和5-羟色胺(5-HT)受体都参与大鼠脊髓节律性运动模式的产生。与单独使用任何一种神经化学物质相比,联合应用这些化学物质在产生类似运动的活动方面更有效。此外,将NMDA应用于在河豚毒素中突触分离的大鼠脊髓运动神经元,会诱导非线性膜行为,导致电压振荡,而这种振荡可被5-HT拮抗剂阻断。然而,与运动节律产生相关的NMDA和5-HT受体相互作用的潜在机制仍有待确定。在本研究中,使用新生大鼠脊髓体外制备物来检查5-HT是否调节NMDA受体介导的非线性膜电压。脊髓运动神经元的全细胞记录表明,5-HT将电流-电压关系中NMDA受体依赖性负斜率电导(RNSC)区域转移到更超极化电位,并增强全细胞内向电流。5-HT对RNSC的影响类似于降低细胞外Mg(2+)浓度对RNSC的影响。结果表明,5-HT可能通过调节NMDA离子通道的Mg(2+)阻断来调节这种形式的膜电压非线性。