Fasting and 17β-estradiol differentially modulate the M-current in neuropeptide Y neurons.
Fasting and 17β-estradiol differentially modulate the M-current in neuropeptide Y neurons.
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DOI：
10.1523/jneurosci.1395-11.2011
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发表时间：
2011-08-17
期刊：
影响因子：
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通讯作者：
Kelly MJ
中科院分区：
文献类型：
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作者：
Roepke TA;Qiu J;Smith AW;Rønnekleiv OK;Kelly MJ
多个K+电导是参与控制能量稳态的许多外周和中枢信号的目标。潜在的K+通道靶标是形成m电流通道的KCNQ亚基，这是一种亚阈值的非失活K+电流，是g蛋白偶联受体的常见靶标。对下丘脑弓形核的GFP （Renilla）标记的NPY神经元进行全细胞记录，使用分离和表征这些缺氧神经元中的m电流的协议。我们在完整雄性和切除卵巢的17β-雌二醇（E2）处理的雌性小鼠中记录了在M电流电压范围内强劲的K+电流，该电流被选择性KCNQ通道阻滞剂XE991（40µM）抑制。由于NPY神经元是供氧的，并且在禁食期间是活跃的，因此在喂食和禁食的雄性小鼠中测量了m电流。禁食使xe991敏感电流减弱了3倍，这与实时荧光定量PCR检测到的KCNQ2和KCNQ3亚基表达降低有关。此外，E2处理使去卵巢雌性小鼠的xe991敏感m电流增加了3倍。e2处理增加了KCNQ5亚基在女性中的表达，但没有增加KCNQ2或KCNQ3亚基的表达。禁食女性通过降低KCNQ2和KCNQ3的表达，至少在一定程度上消除了E2对m电流活性的影响。综上所述，这些数据表明m电流在NPY神经元兴奋性的调节中起着关键作用，并且可能是控制男性和女性能量稳态的神经递质和激素信号的重要细胞靶点。
Multiple K+ conductances are targets for many peripheral and central signals involved in the control of energy homeostasis. Potential K+ channel targets are the KCNQ subunits that form the channels underlying the M-current, a sub-threshold, non-inactivating K+ current that is a common target for G-protein coupled receptors. Whole-cell recordings were made from GFP (Renilla)-tagged NPY neurons from the arcuate nucleus of the hypothalamus using protocols to isolate and characterize the M-current in these orexigenic neurons. We recorded robust K+ currents in the voltage range of the M-current, which were inhibited by the selective KCNQ channel blocker XE991 (40 µM), in both intact males and ovariectomized, 17β-estradiol (E2)-treated females. Since NPY neurons are orexigenic and are active during fasting, the M-current was measured in fed and fasted male mice. Fasting attenuated the XE991-sensitive current by 3-fold which correlated with decreased expression of the KCNQ2 and KCNQ3 subunits as measured with quantitative real-time PCR. Furthermore, E2 treatment augmented the XE991-sensitive M-current by 3-fold in ovariectomized (vs. oil-treated) female mice. E2-treatment increased the expression of the KCNQ5 subunit in females but not KCNQ2 or KCNQ3 subunits. Fasting in females abrogated the effects of E2 on M-current activity, at least in part, by decreasing KCNQ2 and KCNQ3 expression. In summary, these data suggest that the M-current plays a pivotal role in the modulation of NPY neuronal excitability and may be an important cellular target for neurotransmitter and hormonal signals in the control of energy homeostasis in both males and females.