3月10日，美国《神经元》（Neuron ）杂志发表了中科院上海生科院神经所张旭研究员的博士后李开诚、研究生张方雄、李昌林和王烽等共同完成的研究论文，发现了传导痛觉的背根节神经元可以释放一种名为滤泡素抑制素样蛋白1（follistatin-like 1, FSTL1）的蛋白质，通过激动初级感觉传入神经纤维上的钠-钾泵，调节痛觉等感觉信息的传递。
神经元消耗能量，通过钠-钾泵（Na+, K+-ATPase），在细胞浆中浓集钾离子并排出细胞内的钠离子，从而维持细胞膜内外的钠、钾离子浓度梯度，调控细胞膜电位和兴奋性，对调节神经元功能起十分重要的作用。然而，人们一直不清楚除了ATP、钠和钾离子对钠-钾泵的驱动作用，以及一些神经递质、激素通过它们的受体间接地调节钠-钾泵活性以外，身体内是否存在可以直接激动钠-钾浆的物质，并对神经系统功能进行调节。
作者通过一系列的实验发现，传导痛觉的背根节神经元高表达FSTL1，并且通过清亮小泡将FSTL1运输至脊髓内的传入神经终末释放，直接与位于感觉传入神经终末突触前膜上的钠-钾泵α1亚基相结合，增强钠-钾泵活性，使细胞膜超级化，从而对感觉传入神经终末的兴奋性突触传递起抑制性调控作用。课题组与南京大学模式动物研究所高翔教授的科研团队密切合作，制备了当时国内第一例条件式敲除小鼠，在背根节神经元中特异性敲除了FSTL1的基因。研究发现FSTL1条件式敲除小鼠兴奋性突触传递增强，痛觉敏感度增强。因此，FSTL1作为第一个被发现的内源性钠-钾泵激动剂，对于保持正常的躯体感觉是必需的，FSTL1减少则会导致异常痛觉。该发现表明内源性钠-钾泵激动剂可以通过调控突触传递对神经系统功能起重要的影响。
该研究到了中国科学院、科技部973项目、国家自然科学基金等项目的资助。
FSTL1-钠钾泵系统调节突触传递的模式图：膜去极化导致突触囊泡和FSTL1囊泡释放，释放的FSTL1激活位于初级感觉传入神经终末突触前膜上的钠钾泵的a1亚基，使细胞膜超级化，从而对初级感觉传入神经终末的兴奋性突触传递起抑制性调控作用。（生物谷Bioon.com）
生物谷推荐原始出处：
Neuron doi:10.1016/j.neuron.2011.01.022
Follistatin-like 1 Suppresses Sensory Afferent Transmission by Activating Na+,K+-ATPase
Kai-Cheng Li1, 7, Fang-Xiong Zhang1, 2, 7, Chang-Lin Li1, 7, Feng Wang1, 7, Ming-Yan Yu2, Yan-Qing Zhong3, Kai-Hua Zhang1, Ying-Jin Lu1, Qiong Wang3, Xiao-Li Ma1, Jun-Ru Yao1, Jin-Yuan Wang1, Li-Bo Lin4, Mei Han6, Yu-Qiu Zhang6, Rohini Kuner5, Hua-Sheng Xiao4, Lan Bao3, Xiang Gao2, , and Xu Zhang1,
Highlights
FSTL1 is expressed in DRG and secreted via small vesicles at afferent terminals
FSTL1 binds to the α1 subunit of Na+,K+-ATPase and elevates its activity
FSTL1 suppresses the synaptic transmission by activating Na+,K+-ATPase
FSTL1 is required for maintaining the normal threshold of somatic sensation
Summary
Excitatory synaptic transmission is modulated by inhibitory neurotransmitters and neuromodulators. We found that the synaptic transmission of somatic sensory afferents can be rapidly regulated by a presynaptically secreted protein, follistatin-like 1 (FSTL1), which serves as a direct activator of Na+,K+-ATPase (NKA). The FSTL1 protein is highly expressed in small-diameter neurons of the dorsal root ganglion (DRG). It is transported to axon terminals via small translucent vesicles and secreted in both spontaneous and depolarization-induced manners. Biochemical assays showed that FSTL1 binds to the α1 subunit of NKA and elevates NKA activity. Extracellular FSTL1 induced membrane hyperpolarization in cultured cells and inhibited afferent synaptic transmission in spinal cord slices by activating NKA. Genetic deletion of FSTL1 in small DRG neurons of mice resulted in enhanced afferent synaptic transmission and sensory hypersensitivity, which could be reduced by intrathecally applied FSTL1 protein. Thus, FSTL1-dependent activation of NKA regulates the threshold of somatic sensation.
