Chronic dopamine depletion augments the functional expression of K-ATP channels in the rat subthalamic nucleus

[摘要] Symptoms of Parkinson's disease caused by dopamine depletion are associated with burst firing in the subthalamic nucleus (STN). Moreover, regularization or suppression of STN neuronal activity is thought to improve symptoms of Parkinson's disease. We reported recently that N-methyl-D-aspartate (NMDA) receptor stimulation of rat STN neurons evokes ATP-sensitive K+ (K-ATP) current via a Ca2+-and nitric oxide-dependent mechanism. The present studies were done to determine whether or not K-ATP channel function in STN neurons is altered in a model of chronic dopamine depletion. Brain slices were prepared from rats with unilateral dopamine depletion caused by intracerebral 6-hydroxydopamine (6-OHDA) injections. Whole-cell patch-clamp recordings showed that NMDA evoked more outward current at -70 mV and greater positive slope conductance in STN neurons located ipsilateral to 6-OHDA treatment compared to neurons located contralateral. Moreover, extracellular, loose-patch recordings showed that NMDA increased spontaneous firing rate in STN neurons in slices from normal rats, whereas NMDA produced a tolbutamide-sensitive inhibition of firing rate in STN neurons located ipsilateral to 6-OHDA treatment. These results show that K-ATP channel function in STN neurons is up-regulated by chronic dopamine deficiency. We suggest that K-ATP channel activation in the STN might benefit symptoms of Parkinson's disease. Published by Elsevier Ireland Ltd.

[发布日期] 2012-12-07

[关键词] ATP-sensitive K+ channel;Subthalamic nucleus;N-Methyl-D-aspartate;Sulfonylurea;Tolbutamide;Brain slice