Subsecond regulation of striatal dopamine release by pre-synaptic KATP channels.
Subsecond regulation of striatal dopamine release by pre-synaptic KATP channels.
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DOI：
10.1111/j.1471-4159.2011.07358.x
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发表时间：
2011-09
影响因子：
4.7
通讯作者：
Rice ME
中科院分区：
文献类型：
--
作者：
Patel JC;Witkovsky P;Coetzee WA;Rice ME
atp敏感的K+ (KATP)通道由成孔亚基（通常是神经元中的Kir6.2）和调节性磺酰脲受体亚基组成。在背纹状体中，由谷氨酸ampa受体激活产生的活性依赖性H2O2通过KATP通道抑制多巴胺释放。调节性H2O2的来源包括中棘神经元，但不包括多巴胺能轴突。利用豚鼠纹状体切片快速扫描循环伏安法和免疫组织化学，我们确定了H2O2/KATP通道介导抑制的时间窗口，并评估了调节KATP通道是否位于多巴胺能轴突上。比较在没有和存在格列本脲（一种katp通道阻滞剂）或巯基琥珀酸（一种增强内源性H2O2水平的谷胱甘肽过氧化物酶抑制剂）的情况下多巴胺释放的对脉冲抑制，揭示了刺激后500至1000 ms的抑制时间窗口。免疫组织化学显示Kir6.2 katp通道亚基在多巴胺能轴突上的定位。与多巴胺能轴突上存在功能性KATP通道一致，KATP通道打开剂、二氮氧化物和克罗卡林抑制了单脉冲诱发的多巴胺释放。虽然强直性调节多巴胺释放的胆碱能中间神经元也表达KATP通道，但二氮氧化物并没有诱导多巴胺释放的频率反应性增强，而尼古丁受体阻断则没有。总之，这些研究揭示了内源性H2O2作用于多巴胺能轴突上的KATP通道对纹状体多巴胺释放的亚秒调节，包括对脉冲抑制的作用。
ATP-sensitive K+ (KATP) channels are composed of pore-forming subunits, typically Kir6.2 in neurons, and regulatory sulfonylurea receptor subunits. In dorsal striatum, activity-dependent H2O2 produced from glutamatergic AMPA-receptor activation inhibits dopamine release via KATP channels. Sources of modulatory H2O2 include medium spiny neurons, but not dopaminergic axons. Using fast-scan cyclic voltammetry in guinea-pig striatal slices and immunohistochemistry, we determined the time window for H2O2/KATP-channel-mediated inhibition and assessed whether modulatory KATP channels are on dopaminergic axons. Comparison of paired-pulse suppression of dopamine release in the absence and presence of glibenclamide, a KATP-channel blocker, or mercaptosuccinate, a glutathione peroxidase inhibitor that enhances endogenous H2O2 levels, revealed a time window for inhibition of 500 to 1000 ms after stimulation. Immunohistochemistry demonstrated localization of Kir6.2 KATP-channel subunits on dopaminergic axons. Consistent with the presence of functional KATP channels on dopaminergic axons, KATP-channel openers, diazoxide and cromakalim, suppressed single-pulse evoked dopamine release. Although cholinergic interneurons that tonically regulate dopamine release also express KATP channels, diazoxide did not induce the enhanced frequency responsiveness of dopamine release seen with nicotinic-receptor blockade. Together, these studies reveal subsecond regulation of striatal dopamine release by endogenous H2O2 acting at KATP channels on dopaminergic axons, including a role in paired-pulse suppression.
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影响因子：
4.7
作者：
Bao, Li;Patel, Jyoti C.;Rice, Margaret E.
通讯作者：
Rice, Margaret E.
DOI：
10.1073/pnas.1834314100
发表时间：
2003-09-30
影响因子：
11.1
作者：
Avshalumov, MV;Rice, ME
通讯作者：
Rice, ME
影响因子：
5
作者：
Ichinari, K;Kakei, M;Tanaka, H
通讯作者：
Tanaka, H
影响因子：
2.9
作者：
Dunn-Meynell, AA;Rawson, NE;Levin, BE
通讯作者：
Levin, BE
影响因子：
2.9
作者：
DunnMeynell, AA;Routh, VH;Levin, BE
通讯作者：
Levin, BE