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首页> 外文期刊>The European Journal of Neuroscience >An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability.
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An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability.

机译：H218 / AGR16 / Edg-5 / LP（B2）鞘氨醇1-磷酸受体在神经元兴奋性中的重要作用。

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摘要

A wealth of indirect data suggest that the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate (S1P) receptor plays important roles in development. In vitro, it activates several forms of development-related signal transduction and regulates cellular proliferation, differentiation and survival. It is expressed during embryogenesis, and mutation of an H218-like gene in zebrafish leads to profound defects in embryonic development. Nevertheless, the in vivo functions served by H218 signalling have not been directly investigated. We report here that mice in which the H218 gene has been disrupted are unexpectedly born with no apparent anatomical or physiological defects. In addition, no abnormalities were observed in general neurological development, peripheral axon growth or brain structure. However, between 3 and 7 weeks of age, H218(-/-) mice have seizures which are spontaneous, sporadic and occasionally lethal. Electroencephalographic abnormalities were identified both during and between the seizures. At a cellular level, whole-cell patch-clamp recordings revealed that the loss of H218 leads to a large increase in the excitability of neocortical pyramidal neurons. Therefore, H218 plays an essential, unanticipated and functionally important role in the proper development and/or mediation of neuronal excitability.
机译：大量的间接数据表明，H218 / AGR16 / Edg-5 / LP（B2）鞘氨醇1-磷酸（S1P）受体在发育中起重要作用。在体外，它激活几种形式的与发育相关的信号转导，并调节细胞的增殖，分化和存活。它在胚胎发生过程中表达，斑马鱼中H218样基因的突变导致胚胎发育中的严重缺陷。然而，尚未直接研究H218信号传导所服务的体内功能。我们在这里报告，其中H218基因已被破坏的小鼠出乎意料地出生，没有明显的解剖或生理缺陷。此外，在一般神经系统发育，周围轴突生长或脑结构中未观察到异常。但是，在3至7周龄之间，H218（-/-）小鼠的癫痫发作是自发的，偶发的，偶有致命性。在癫痫发作期间和发作之间均发现脑电图异常。在细胞水平上，全细胞膜片钳记录显示，H218的丢失导致新皮层锥体神经元的兴奋性大大提高。因此，H218在神经元兴奋性的正确发育和/或介导中起着至关重要的，意想不到的和功能上重要的作用。

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