钠离子通道疾病及其抑制剂生物学功能研究进展

Progress in sodium channelopathies and biological functions of voltage-gated sodium channel blockers

摘要:

电压门控型钠离子通道 (Voltage-gated sodium channel, VGSC) 广泛分布于兴奋性细胞，是电信号扩大和传导的主要介质，在神经细胞以及心肌细胞兴奋传导等方面发挥重要作用。钠离子通道结构和功能的异常会改变细胞的兴奋性，从而导致多种疾病的发生，如神经性疼痛、癫痫，以及心律失常等。目前临床上多采用钠离子通道抑制剂治疗上述疾病。近些年，研究人员陆续从动物的毒液中分离纯化出具有调控钠离子通道功能的神经毒素。这些神经毒素多为化合物或小分子多肽。现已有医药研发公司将这些天然的神经毒素进行定向设计改造成钠离子通道靶向药物用于临床疾病的治疗。此外，来源于七鳃鳗Lampetra japonica口腔腺的富含半胱氨酸分泌蛋白 (Cysteine-rich buccal gland protein，CRBGP) 也首次被证明能够抑制海马神经元和背根神经元的钠离子电流。以下针对钠离子通道疾病及其抑制剂生物学功能的最新研究进展进行分析归纳。

Abstract:

Voltage-gated sodium channels (VGSCs), which are widely distributed in the excitable cells, are the primary mediators of electrical signal amplification and propagation. They play important roles in the excitative conduction of the neurons and cardiac muscle cells. The abnormalities of the structures and functions of VGSCs can change the excitability of the cells, resulting in a variety of diseases such as neuropathic pain, epilepsy and arrhythmia. At present, some voltage-gated sodium channel blockers are used for treating those diseases. In the recent years, several neurotoxins have been purified from the venom of the animals, which could inhibit the current of the voltage-gated sodium channels. Usually, these neurotoxins are compounds or small peptides that have been further designed and modified for targeted drugs of sodium channelopathies in the clinical treatment. In addition, a novel cysteine-rich secretory protein (CRBGP) has been isolated and purified from the buccal gland of the lampreys (Lampetra japonica), and it could inhibit the Na+ current of the hippocampus and dorsal root neurons for the first time. In the present study, the progress of the sodium channelopathies and the biological functions of voltage-gated sodium channel blockers are analyzed and summarized.