Ca2+ influx through NMDA-gated channels activates ATP-sensitive K+ currents through a nitric oxide-cGMP pathway in subthalamic neurons.
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.
Department of Neurology, Oregon Health and Science University, Portland, Oregon 97239, USA. shenk@ohsu.edu
Ke-Zhong
KZ
Shen
Steven W
SW
Johnson
D000200:Action Potentials; D000818:Animals; D001464:Barium / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D015640:Ion Channel Gating; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism*; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000378:metabolism*
D054086:KATP Channels; D001464:Barium; D009569:Nitric Oxide; D016202:N-Methylaspartate; D006152:Cyclic GMP; D002118:Calcium