Key Laboratory of Neurological Disease, Ministry of Education, Huazhong University of Science and Technology Tongji Medical College, Wuhan, 430030 China.
J Neurosci. 2013 May 15;33(20):8861-5. doi: 10.1523/JNEUROSCI.5686-12.2013.
EPAC (Exchange Proteins Activated by cAMP) regulates glutamate transmitter release in the central neurons, but a role underlying this regulation has yet to be identified. Here we show that EPAC binds directly to the intracellular loop of an ATP-sensitive potassium (KATP) channel type-1 sulfonylurea receptor (SUR1) receptor consisting of amino acids 859-881 (SUR1(859-881)). Ablation of EPAC or expression of SUR1(859-881), which intercepts EPAC-SUR1 binding, increases the open probability of KATP channels consisting of the Kir6.1 subunit and SUR1. Opening of KATP channels inhibits glutamate release and reduces seizure vulnerability in adult mice. Therefore, EPAC interaction with SUR1 controls seizure susceptibility and possibly acts via regulation of glutamate release.
环核苷酸交换因子（EPAC）调节中枢神经元中的谷氨酸递质释放，但这种调节的作用尚待确定。本文中，作者表明 EPAC 可直接与由氨基酸 859-881 组成的三磷酸腺苷敏感钾（KATP）通道型 1 磺酰脲受体（SUR1）的细胞内环结合（SUR1(859-881)）。EPAC 的缺失或表达 SUR1(859-881)，可以阻断 EPAC-SUR1 的结合，增加由 Kir6.1 亚基和 SUR1 组成的 KATP 通道的开放概率。KATP 通道的开放抑制谷氨酸的释放，并降低成年小鼠的癫痫易感性。因此，EPAC 与 SUR1 的相互作用控制着癫痫易感性，可能通过调节谷氨酸的释放起作用。
