Genetic loss of HCN1 channels is exciting, but is it epileptic?
Genetic loss of HCN1 channels is exciting, but is it epileptic?
复制标题
HCN1 通道的遗传缺失令人兴奋，但它会导致癫痫吗？
DOI：
10.1111/j.1535-7511.2009.01352.x
复制
发表时间：
2010
影响因子：
3.6
通讯作者：
Poolos,NicholasP
中科院分区：
文献类型：
--
作者：
Poolos,NicholasP
树突状HCN 1亚单位的缺失增强了皮质兴奋性和癫痫发生。Huang Z，步行者MC，Shah MM.J Neurosci 2009;29（35）：10979-10988。内嗅皮层（EC）和海马锥体细胞树突的超极化激活阳离子非选择性1（HCN 1）可塑性是颞叶癫痫的一个显著特征。然而，其重要性仍未确定。我们证明了成年HCN 1基因缺失小鼠对红藻氨酸诱导的癫痫发作更敏感。在用抗惊厥药终止这些之后，小鼠也以比其野生型同窝小鼠显著更快的速率发生自发性行为癫痫发作。这种更大的癫痫易感性伴随着增加自发活动在HCN 1-/-EC层III神经元。这些神经元中的树突状细胞也被消融。因此，HCN 1-/-树突更兴奋，尽管有显着更超极化静息膜电位（RMP）。此外，EPSP的整合大大增强，在正常RMP下，50 Hz的EPSP序列在HCN 1-/-神经元中产生动作电位。由于这种增强的锥体细胞兴奋性，自发EPSC频率ontoHCN 1-/-神经元是相当大的比野生型，导致正常的兴奋性和抑制性突触活动之间的不平衡。这些结果表明，树突状HCN通道可能在调节皮质锥体细胞兴奋性中发挥关键作用。此外，这些研究结果表明，在癫痫发生过程中树突HCN 1亚基表达的减少可能会促进疾病。
Loss of Dendritic HCN1 Subunits Enhances Cortical Excitability and Epileptogenesis.Huang Z, Walker MC, Shah MM.J Neurosci2009;29(35):10979–10988. Hyperpolarization-activated cation nonselective 1 (HCN1) plasticity in entorhinal cortical (EC) and hippocampal pyramidal cell dendrites is a salient feature of temporal lobe epilepsy. However, the significance remains undetermined. We demonstrate that adult HCN1 null mice are more susceptible to kainic acid-induced seizures. After termination of these with an anticonvulsant, the mice also developed spontaneous behavioral seizures at a significantly more rapid rate than their wild-type littermates. This greater seizure susceptibility was accompanied by increased spontaneous activity inHCN1-/-EC layer III neurons. DendriticIhin these neurons was ablated, too. Consequentially,HCN1-/-dendrites were more excitable, despite having significantly more hyperpolarized resting membrane potentials (RMPs). In addition, the integration of EPSPs was enhanced considerably such that, at normal RMP, a 50 Hz train of EPSPs produced action potentials inHCN1-/-neurons. As a result of this enhanced pyramidal cell excitability, spontaneous EPSC frequency ontoHCN1-/-neurons was considerably greater than that onto wild types, causing an imbalance between normal excitatory and inhibitory synaptic activity. These results suggest that dendritic HCN channels are likely to play a critical role in regulating cortical pyramidal cell excitability. Furthermore, these findings suggest that the reduction in dendritic HCN1 subunit expression during epileptogenesis is likely to facilitate the disorder.