Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy.
Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy.
复制标题
钾通道调节的变化可能是妊娠晚期催产素神经元后超极化可塑性的基础。
DOI：
10.1152/jn.00608.2017
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发表时间：
2018
影响因子：
2.5
通讯作者：
Armstrong,WilliamE
中科院分区：
文献类型：
--
作者：
Wang,Lie;Chandaka,GiriKumar;Foehring,RobertC;Callaway,JosephC;Armstrong,WilliamE
催产素（OT）神经元表现出更大的后超极化（AHPs）的尖峰列车在妊娠后期和哺乳期，这些神经元的时候，在爆发和释放更多的OT与劳动和哺乳。由SK通道介导的钙依赖性AHP显示出这种可塑性，并且当通道复合物被酪蛋白激酶2（CK 2）磷酸化时减少，并且当被蛋白磷酸酶（PP）2A去磷酸化时增加，通过改变Ca 2+敏感性。我们比较了用4，5，6，7-四溴苯并三唑（TBB）抑制CK 2或用冈田酸（OA）抑制PP 1-PP 2A后，视上OT神经元中的AHP电流，以确定这些酶在AHP可塑性中的作用，重点关注代表SK介导的中等AHP（ImAHP）的100 ms处的峰值电流。在处女和两组妊娠大鼠[胚胎日（E18-19，或E20-21）]的切片中，用3-，10-和17-尖峰序列（20 Hz）诱发ImAHPs。与两组妊娠动物相比，TBB在3-spike trains中最大程度地增加了处女的ImAHP。处女和E20-21大鼠之间的差异也是明显的10个尖峰列车，但在ImAHPs的增加是相似的17个尖峰列车组。相比之下，OA虽然在所有病例中持续降低ImAHPin，但在组间没有显示出差异效应。在Western印迹中，在E20-21大鼠的视上裂解物中发现CK 2 α、CK 2 β、PP 2A-A、PP 2A-B和PP 2A-C，并且CK 2 α和CK 2 β的表达减少。免疫共沉淀显示钙调素、CK 2 α和PP 2A-C与SK 3蛋白结合。结果表明，在妊娠晚期，SK 3相关的CK 2 α下调可能会增加SK钙调素（Ca 2+）传感器对ImAHP的敏感性，新&值得注意的是，这篇文章首次证明了妊娠期间催产素神经元尖峰后超极化的增强可能与小电导Ca 2+激活钾通道（SK）的下调有关。钙调蛋白结合蛋白酪蛋白激酶2，其磷酸化SK通道复合物并降低其Ca 2+敏感性。
Oxytocin (OT) neurons exhibit larger afterhyperpolarizations (AHPs) following spike trains during late pregnancy and lactation, times when these neurons fire in bursts and release more OT associated with labor and lactation. Calcium-dependent AHPs mediated by SK channels show this plasticity, and are reduced when the channel complex is phosphorylated by casein kinase 2 (CK2), and increased when dephosphorylated by protein phosphatase (PP)2A, by altering Ca2+sensitivity. We compared AHP currents in supraoptic OT neurons after CK2 inhibition with 4,5,6,7-tetrabromobenzotriazole (TBB), or PP1-PP2A inhibition with okadaic acid (OA), to determine the roles of these enzymes in AHP plasticity, focusing on the peak current at 100 ms representing the SK-mediated, medium AHP (ImAHP). In slices from virgin and two groups of pregnant rats [embryonic days (E18–19, or E20–21], ImAHPs were evoked with 3-, 10-, and 17-spike trains (20 Hz). With 3-spike trains, TBB increased the ImAHPto the greatest extent in virgin compared with both groups of pregnant animals. A difference between virgins and E20–21 rats was also evident with a 10-spike train but the increases in ImAHPs were similar among groups with 17-spike trains. In contrast, OA, while consistently reducing the ImAHPin all cases, showed no differential effects among groups. In Western blots, CK2α, CK2β, PP2A-A, PP2A-B, and PP2A-C were found in supraoptic lysates, and expression of CK2α and CK2β was reduced in E20–21 rats. Coimmunoprecipitation revealed that calmodulin, CK2α, and PP2A-C were associated with SK3 protein. The results suggest that a downregulation of SK3-associated CK2α during late pregnancy may increase the sensitivity of the SK calmodulin (Ca2+) sensor for ImAHP, contributing to the enhanced ImAHP.NEW & NOTEWORTHYThe article demonstrates for the first time that enhancement in spike afterhyperpolarizations in oxytocin neurons during pregnancy may be related to a downregulation in the small-conductance Ca2+-activated potassium channels (SK)/calmodulin binding protein casein kinase 2, which phosphorylates the SK channel complex and reduces its Ca2+sensitivity.