Ca2+ influx through NMDA-gated channels activates ATP-sensitive K+ currents through a nitric oxide-cGMP pathway in subthalamic neurons.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Ke-Zhong Shen, Steven W Johnson

Abstract

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.

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Citations

May 3, 2011·Analytical and Bioanalytical Chemistry·Simon A JamesStephen W Wilkins
Sep 10, 2014·The Journal of Clinical Investigation·Ming-Kai PanChung-Chin Kuo
Jan 22, 2013·The Journal of Pharmacology and Experimental Therapeutics·Ke-Zhong Shen, Steven W Johnson
Jan 8, 2016·Trends in Endocrinology and Metabolism : TEM·Silke Otter, Eckhard Lammert
Feb 13, 2016·Scientific Reports·Chunmei LiDavid L Kaplan
Jun 16, 2015·Frontiers in Neuroscience·Alekhya MandaliAhmed A Moustafa
Mar 7, 2014·Schizophrenia Research·Bruna da Silveira PaulsenStevens Kastrup Rehen
Jul 16, 2020·The Journal of Pharmacology and Experimental Therapeutics·Anne Gresch, Martina Düfer
Aug 27, 2018·BMC Research Notes·Ryota ImaiKenju Shimomura

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