Department of Neurology, Oregon Health and Science University, Portland, Oregon 97239, USA.
J Neurosci. 2010 Feb 3;30(5):1882-93. doi: 10.1523/JNEUROSCI.3200-09.2010.
Excessive burst firing of action potentials in subthalamic nucleus (STN) neurons has been correlated with the bradykinesia and rigidity seen in Parkinson's disease. Consequently, there is much interest in characterizing mechanisms that promote burst firing, such as the regulation of NMDA receptor function. Using whole-cell recording techniques in rat brain slices, we report that inward currents evoked by NMDA are greatly potentiated by ATP-sensitive K(+) (K-ATP) channel blocking agents in STN neurons but not in dopamine neurons in the substantia nigra. Moreover, we found that the ability of NMDA to evoke K-ATP current was blocked by inhibitors of nitric oxide synthase, guanylyl cyclase, and calcium/calmodulin. By altering firing patterns of STN neurons, this NMDA/K-ATP interaction may exert an important influence on basal ganglia output and thereby affect the clinical expression of Parkinson's disease.
在帕金森病中，与运动徐缓、僵直相关的现象与丘脑底核（STN）神经元的动作电位过度爆发有关。因此，人们对描述促进爆发性放电的机制很感兴趣，如 NMDA 受体功能的调节。在大鼠脑片上使用全细胞膜片钳技术，我们报告在 STN 神经元中，由 NMDA 引发的内向电流会被三磷酸腺苷敏感的钾（K-ATP）通道阻断剂大大增强，但在黑质多巴胺神经元中则不会。此外，我们发现，NMDA 引发 K-ATP 电流的能力被一氧化氮合酶、鸟苷酸环化酶和钙/钙调蛋白抑制剂阻断。通过改变 STN 神经元的放电模式，这种 NMDA/K-ATP 相互作用可能对基底节输出产生重要影响，从而影响帕金森病的临床表型。
