Hahn Junghyun, Kullmann Paul H M, Horn John P, Levitan Edwin S
Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
J Neurosci. 2006 May 10;26(19):5240-7. doi: 10.1523/JNEUROSCI.4976-05.2006.
Activation of D2 autoreceptors on midbrain dopamine neurons has been shown previously to acutely open K+ channels to inhibit intrinsically generated pacemaker activity. Here we report that D2 autoreceptors act chronically to produce an opposite action: to increase the speed and regularity of repetitive action potential firing. Voltage-, current-, and dynamic-clamp experiments, using conventional whole-cell and perforated patch-clamp recording, with cultured rat midbrain dopamine neurons show that a change in the number of functional A-type K+ channels alters firing rate and susceptibility to irregularity produced by other channels. cAMP and protein kinase A mediate the long-term action of D2 receptors in a manner that counters the short-term effect of this signaling pathway on K+ channel gating. We conclude that D2 autoreceptors, in addition to mediating acute negative feedback, are responsible for long-term enhancement of the rate and fidelity of dopamine neuron pacemaker activity.
先前的研究表明，中脑多巴胺神经元上的D2自身受体激活可急性打开钾离子通道，以抑制内在产生的起搏活动。在此我们报告，D2自身受体长期作用会产生相反的效应：提高重复动作电位发放的速度和规律性。使用传统全细胞和穿孔膜片钳记录对培养的大鼠中脑多巴胺神经元进行的电压、电流和动态钳实验表明，功能性A 型钾离子通道数量的变化会改变发放频率以及对其他通道产生的不规则性的易感性。环磷酸腺苷（cAMP）和蛋白激酶A以一种抵消该信号通路对钾离子通道门控短期效应的方式介导D2受体的长期作用。我们得出结论，D2自身受体除了介导急性负反馈外，还负责长期增强多巴胺神经元起搏活动的频率和保真度。
