文章基本信息

标题：Inhibitory synaptic transmission is impaired at higher extracellular Ca ²⁺ concentrations in Scn1a ^+/− mouse model of Dravet syndrome
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作者：Kouya Uchino ; Hiroyuki Kawano ; Yasuyoshi Tanaka 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2021
卷号：11
DOI：10.1038/s41598-021-90224-4
语种：English
出版社：Springer Nature
摘要：Dravet syndrome (DS) is an intractable form of childhood epilepsy that occurs in infancy. More than 80% of all patients have a heterozygous abnormality in the SCN1A gene, which encodes a subunit of Na + channels in the brain. However, the detailed pathogenesis of DS remains unclear. This study investigated the synaptic pathogenesis of this disease in terms of excitatory/inhibitory balance using a mouse model of DS. We show that excitatory postsynaptic currents were similar between Scn1a knock-in neurons ( Scn1a +/− neurons) and wild-type neurons, but inhibitory postsynaptic currents were significantly lower in Scn1a +/− neurons. Moreover, both the vesicular release probability and the number of inhibitory synapses were significantly lower in Scn1a +/− neurons compared with wild-type neurons. There was no proportional increase in inhibitory postsynaptic current amplitude in response to increased extracellular Ca 2+ concentrations. Our study revealed that the number of inhibitory synapses is significantly reduced in Scn1a +/− neurons, while the sensitivity of inhibitory synapses to extracellular Ca 2+ concentrations is markedly increased. These data suggest that Ca 2+ tethering in inhibitory nerve terminals may be disturbed following the synaptic burst, likely leading to epileptic symptoms.