SK channels participate in the formation of after burst hyperpolarization and partly inhibit the burst strength of epileptic ictal discharges.

SK channels participate in the formation of after burst hyperpolarization and partly inhibit the burst strength of epileptic ictal discharges.
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SK通道参与突发后超极化的形成并部分抑制癫痫发作放电的突发强度

DOI:
10.3892/mmr.2017.8068
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发表时间:
2018-01
影响因子:
3.4
通讯作者:
Wang Y
Wang Y
中科院分区:
医学4区
文献类型:
--
作者:
Huang Y;Liu X;Wang G;Wang Y

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癫痫是一种常见的中枢神经系统疾病。强直性痉挛和惊厥是癫痫发作期间表现出的主要症状。然而,大多数患者在严重癫痫发作后出现显著的癫痫发作后沉默;这种爆发间期的潜在分子神经机制尚不清楚。本研究的目的是揭示钙激活钾通道在癫痫发作间期沉默期的作用和地位。用环噻嗪(CTZ)建立大鼠海马神经元惊厥模型,应用膜片钳技术记录癫痫发作后超极化(ABH)活动。通过比较超极化的幅度和持续时间,本研究分析了不同浓度的CTZ治疗时癫痫样爆发和ABH之间的关系。此外,apamin和iberiotoxin用于药理试验。在动物身上重复CTZ实验时,还进行了颅内脑电图(EEG)记录。实验结果表明,高剂量CTZ处理后ABH增大,且与癫痫样爆发活动增强有关,提示ABH与癫痫样爆发呈正相关。Apamin是小电导钙激活钾(SK)通道的拮抗剂,可降低ABH的幅度;然而,降低ABH与增强的爆发活性(爆发概率和爆发强度)相关。这些结果揭示了SK通道在ABH形成和抑制爆发活动中的重要作用。伊比利亚毒素是大电导钙激活钾(BK)通道的拮抗剂,对ABH和爆发活动无显着影响。此外,爆发持续时间和ABH参数之间呈正相关。细胞内钙螯合剂损害ABH的幅度,但是,它不影响的爆发参数。大鼠皮层脑电图记录也显示出类似的癫痫爆发持续时间与爆发后抑郁之间的正相关。总的来说,这些结果表明,ABH可能在生理反馈系统,以减少强度的癫痫过度兴奋,一个过程中,SK通道是重要的。
Epilepsy is a common disease of the central nervous system. Tetanic spasms and convulsions are the key symptoms exhibited during epileptic seizures. However, the majority of patients have a significant post-seizure silence following a serious seizure; the underlying molecular neural mechanisms in this burst interval are unclear. The aim of the present study was to reveal the effect and role of calcium-activated potassium channels during this seizure interval silence period. Cyclothiazide (CTZ) was used to establish the seizure model in rat hippocampal cultured neurons, then the after-burst hyperpolarization (ABH) activities were recorded using the patch clamp technique. By comparing the amplitude and duration of hyperpolarizations, the present study analyzed the association between epileptiform bursts and ABHs when treated with different concentrations of CTZ. In addition, apamin and iberiotoxin were used for pharmacological tests. An intracranial electroencephalogram (EEG) recording was also performed when the CTZ experiments were repeated on animals. The experimental results revealed that treatment with high levels of CTZ induced larger ABHs and was associated with stronger burst activities, which suggested a positive correlation between ABH and epileptiform burst. Apamin, an antagonist of small conductance calcium-activated potassium (SK) channels, decreased the amplitude of ABH; however, reduced ABH was associated with enhanced burst activity, in burst probability and burst strength. These results revealed an important role of SK channels in the formation of ABH and in the inhibition of burst activity. Iberiotoxin, an antagonist of big conductance calcium-activated potassium (BK) channels, had no significant effect on ABH and burst activity. In addition, a positive correlation was identified between burst duration and ABH parameters. An intracellular calcium chelator impaired the amplitude of ABH; however, it did not affect the burst parameters. The rat cortical EEG recordings also exhibited a similar positive correlation between the duration of epileptic burst and after burst depression. Collectively, the results indicate that ABH may serve in the physiological feedback system to reduce the strength of epileptic hyperexcitation, a process in which SK channels are important.
DOI: 10.1016/j.seizure.2015.08.004
发表时间: 2015-11
期刊: Seizure
影响因子: --
作者:
Afra P;Jouny CC;Bergey GK
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发表时间: 2006-12-01
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Fernandez de Sevilla, David;Garduno, Julieta;Buno, Washington
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DOI: 10.1073/pnas.2133370100
发表时间: 2003-10-28
影响因子: 11.1
作者:
Deng, LB;Chen, G
通讯作者: Chen, G