Regulation of action potential delays via voltage-gated potassium Kv1.1 channels in dentate granule cells during hippocampal epilepsy.
Regulation of action potential delays via voltage-gated potassium Kv1.1 channels in dentate granule cells during hippocampal epilepsy.
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DOI：
10.3389/fncel.2013.00248
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发表时间：
2013
影响因子：
5.3
通讯作者：
Wolfart J
中科院分区：
文献类型：
--
作者：
Kirchheim F;Tinnes S;Haas CA;Stegen M;Wolfart J
齿状回颗粒 (DG) 细胞的动作电位 (AP) 反应必须受到严格调节才能维持海马功能。然而，哪些离子通道控制 DG 细胞的响应延迟尚不清楚。在某些神经元类型中，尖峰潜伏期受到树突毒素 (DTX) 敏感延迟电流 (ID) 的影响，该延迟电流是由 Kv1 家族 Kv1.1-6 的电压门控 K+ (Kv) 通道的未识别组合介导的。在 DG 细胞中，ID 尚未被表征，其分子基础未知。成熟 DG 细胞的反应表型通常被认为是同质的，但内在的可塑性可能会发生，特别是在过度兴奋的情况下，例如颞叶癫痫 (TLE) 期间。在这项研究中，我们通过在急性脑切片中结合使用短杆菌肽穿孔膜片钳记录和单细胞逆转录酶定量聚合酶链式反应（SC RT-qPCR）实验，检查了 DG 细胞和潜在离子通道分子的响应延迟。使用由海马内红藻氨酸 (KA) 注射组成的 TLE 体内小鼠模型来检查癫痫相关的可塑性。 DG 细胞的反应延迟对 DTX 敏感，并且在注射 KA 的海马中显着增加； Kv1.1 mRNA 升高了 10 倍，并且反应延迟与单细胞水平上的 Kv1.1 mRNA 丰度相关。其他 Kv1 亚基的 mRNA 水平没有表现出明显的变化。 Kv1.1 免疫标记在 KA DG 细胞中增强。对 ID 的生物物理特性和 DG 细胞群内的延迟异质性进行了表征。使用器官型海马切片培养物 (OHC)（其中 KA 孵育也诱导 ID 上调），测试了 DG 细胞的稳态可逆性和神经保护潜力。总之，DG 细胞的 AP 时间通过 Kv1.1 亚基转录的缩放得到有效控制。通过这种抗癫痫机制，DG 细胞在过度兴奋期间延迟其反应。
Action potential (AP) responses of dentate gyrus granule (DG) cells have to be tightly regulated to maintain hippocampal function. However, which ion channels control the response delay of DG cells is not known. In some neuron types, spike latency is influenced by a dendrotoxin (DTX)-sensitive delay current (ID) mediated by unidentified combinations of voltage-gated K+ (Kv) channels of the Kv1 family Kv1.1–6. In DG cells, the ID has not been characterized and its molecular basis is unknown. The response phenotype of mature DG cells is usually considered homogenous but intrinsic plasticity likely occurs in particular in conditions of hyperexcitability, for example during temporal lobe epilepsy (TLE). In this study, we examined response delays of DG cells and underlying ion channel molecules by employing a combination of gramicidin-perforated patch-clamp recordings in acute brain slices and single-cell reverse transcriptase quantitative polymerase chain reaction (SC RT-qPCR) experiments. An in vivo mouse model of TLE consisting of intrahippocampal kainate (KA) injection was used to examine epilepsy-related plasticity. Response delays of DG cells were DTX-sensitive and strongly increased in KA-injected hippocampi; Kv1.1 mRNA was elevated 10-fold, and the response delays correlated with Kv1.1 mRNA abundance on the single cell level. Other Kv1 subunits did not show overt changes in mRNA levels. Kv1.1 immunolabeling was enhanced in KA DG cells. The biophysical properties of ID and a delay heterogeneity within the DG cell population was characterized. Using organotypic hippocampal slice cultures (OHCs), where KA incubation also induced ID upregulation, the homeostatic reversibility and neuroprotective potential for DG cells were tested. In summary, the AP timing of DG cells is effectively controlled via scaling of Kv1.1 subunit transcription. With this antiepileptic mechanism, DG cells delay their responses during hyperexcitation.
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影响因子：
25
作者：
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通讯作者：
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影响因子：
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