Decreased A-currents in hippocampal dentate granule cells after seizure-inducing hypoxia in the immature rat.
Decreased A-currents in hippocampal dentate granule cells after seizure-inducing hypoxia in the immature rat.
复制标题
在未成熟大鼠中癫痫发作缺氧后，海马齿状颗粒细胞中的A-潮流减少。
DOI：
10.1111/epi.12150
复制
发表时间：
2013-07
期刊：
影响因子：
5.6
通讯作者：
Sanchez RM
中科院分区：
文献类型：
--
作者：
Peng BW;Justice JA;He XH;Sanchez RM
脑缺氧是新生儿癫痫发作的主要原因，并可导致癫痫。在许多实验模型中，齿状回的病理解剖学和生理学变化与癫痫发生相关，因为该区域被广泛认为是边缘系统癫痫发作传播的门控。然而，缺氧诱导癫痫发作对未成熟齿状回的影响尚未得到广泛的研究。在出生后第10天，大鼠幼仔通过全身缺氧（5-7% O2，15分钟）诱导癫痫发作。采用全细胞电压钳技术观察缺氧后1-17天海马脑片齿状回颗粒细胞A型钾电流。癫痫引起的缺氧导致降低最大IA振幅在第一周内记录的齿状颗粒细胞，但不是在以后的时间缺氧处理后。IA振幅的降低与激活或失活清除的电压依赖性变化或对4-氨基吡啶（4-AP）抑制的敏感性变化无关。然而，与IA在塑造放电模式中的作用一致，我们在缺氧组中观察到从超极化电位注入去极化电流的第一个尖峰的潜伏期显著降低。这些差异与静息膜电位或输入电阻的变化无关，并通过应用10 mM 4-AP消除。由于IA的作用，以减缓动作电位放电，减少IA可能有助于长期海马病理新生儿脑缺血诱导缺氧后，增加DG细胞兴奋性的活动依赖性海马成熟的关键窗口。
Cerebral hypoxia is a major cause of neonatal seizures, and can lead to epilepsy. Pathological anatomical and physiological changes in the dentate gyrus have been associated with epileptogenesis in many experimental models, as this region is widely believed to gate the propagation of limbic seizures. However, the consequences of hypoxia-induced seizures for the immature dentate gyrus have not been extensively examined. Seizures were induced by global hypoxia (5–7% O2 for 15 minutes) in rat pups on postnatal day 10. Whole-cell voltage-clamp recordings were used to examine A-type potassium currents (IA) in dentate granule cells in hippocampal slices obtained 1–17 days after hypoxia treatment. Seizure-inducing hypoxia resulted in decreased maximum IA amplitude in dentate granule cells recorded within the first week but not at later times after hypoxia treatment. The decreased IA amplitude was not associated with changes in the voltage-dependence of activation or inactivation removal, or in sensitivity to inhibition by 4-aminopyridine (4-AP). However, consistent with the role of IA in shaping firing patterns, we observed in the hypoxia group a significantly decreased latency to first spike with depolarizing current injection from hyperpolarized potentials. These differences were not associated with changes in resting membrane potential or input resistance, and were eliminated by application of 10 mM 4-AP. Given the role of IA to slow action potential firing, decreased IA could contribute to long-term hippocampal pathology after neonatal seizure-inducing hypoxia by increasing DG cell excitability during a critical window of activity-dependent hippocampal maturation.
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DOI：
10.1523/jneurosci.1734-08.2008
发表时间：
2008-08-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Rakhade SN;Zhou C;Aujla PK;Fishman R;Sucher NJ;Jensen FE
通讯作者：
Jensen FE
影响因子：
11.2
作者：
JENSEN, FE;APPLEGATE, CD;BURCHFIEL, JL
通讯作者：
BURCHFIEL, JL
影响因子：
5.5
作者：
Korngreen, A;Sakmann, B
通讯作者：
Sakmann, B
影响因子：
56.9
作者：
Bernard, C;Anderson, A;Johnston, D
通讯作者：
Johnston, D
影响因子：
5.5
作者：
Bekkers, JM
通讯作者：
Bekkers, JM