Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability
Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability
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DOI：
10.1073/pnas.0705487105
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发表时间：
2008-01-08
影响因子：
11.1
通讯作者：
Huebner, Christian A.
中科院分区：
文献类型：
--
作者：
Jacobs, Stefan;Ruusuvuori, Eva;Huebner, Christian A.
SLC4碳酸氢盐转运体家族成员参与溶质转运和pH动态平衡。在这里，我们报告了破坏S1c4a10基因，它编码了Na+偶联的Cl-HCO3-交换器Slc4a10(NCBE)，显著减少了小鼠的脑室体积，并防止了致命的癫痫发作。在脉络丛上皮细胞中，SLC4a10定位于基底膜。在KO小鼠中，这些细胞表现出从酸负荷中恢复的减弱。5lc4a10在神经元中也有表达。在海马区，SLC4a10蛋白在CA3锥体细胞中含量丰富。在CA3区，丙酸诱导的细胞内酸化和4-氨基吡啶诱导的网络活动的衰减在KO小鼠中延长。我们的数据表明，SLC4a10参与了神经元pH和兴奋性的控制，并可能参与脑脊液的分泌。因此，SLC4a10是治疗癫痫或高颅压的一个很有前途的药理靶点。
Members of the SLC4 bicarbonate transporter family are involved in solute transport and pH homeostasis. Here we report that disrupting the S1c4a10 gene, which encodes the Na+-coupled Cl--HCO3- exchanger Slc4a10 (NCBE), drastically reduces brain ventricle volume and protects against fatal epileptic seizures in mice. In choroid plexus epithelial cells, Slc4a10 localizes to the basolateral membrane. These cells displayed a diminished recovery from an acid load in KO mice. 5lc4a10 also was expressed in neurons. Within the hippocampus, the Slc4a10 protein was abundant in CA3 pyramidal cells. In the CA3 area, propionate-induced intracellular acidification and attenuation of 4-aminopyridine-induced network activity were prolonged in KO mice. Our data indicate that Slc4a10 is involved in the control of neuronal pH and excitability and may contribute to the secretion of cerebrospinal fluid. Hence, Slc4a10 is a promising pharmacological target for the therapy of epilepsy or elevated intracranial pressure.