Abstract：
Maintaining the correct ionic gradient from extracellular to intracellular space via several membrane-bound transporters is critical for maintaining overall cellular homeostasis. One of these transporters is the transient receptor potential (TRP) channel family that consists of six putative transmembrane segments systemically expressed in mammalian tissues. Upon the activation of TRP channels by brain disease, several cations are translocated through TRP channels. Brain disease, especially ischemic stroke, epilepsy, and traumatic brain injury, triggers the dysregulation of ionic gradients and promotes the excessive release of neuro-transmitters and zinc. The divalent metal cation zinc is highly distributed in the brain and is specifically located in the pre-synaptic vesicles as free ions, usually existing in cytoplasm bound with metallothionein. Although adequate zinc is essential for regulating diverse physiological functions, the brain-disease-induced excessive release and translocation of zinc causes cell damage, including oxidative stress, apoptotic cascades, and disturbances in energy metabolism. Therefore, the regulation of zinc homeostasis following brain disease is critical for the prevention of brain damage. In this review, we summarize recent experimental research findings regarding how TRP channels (mainly TRPC and TRPM) and zinc are regulated in animal brain-disease models of global cerebral ischemia, epilepsy, and traumatic brain injury. The blockade of zinc translocation via the inhibition of TRPC and TRPM channels using known channel antagonists, was shown to be neuroprotective in brain disease. The regulation of both zinc and TRP channels may serve as targets for treating and preventing neuronal death.
摘要：
通过几种膜结合转运蛋白维持从细胞外到细胞内空间的正确离子梯度对于维持整体细胞稳态至关重要。这些转运蛋白之一是瞬时受体电位(TRP)通道家族,其由在哺乳动物组织中全身表达的六个推定的跨膜区段组成。当TRP通道被脑部疾病激活时，几种阳离子通过TRP通道易位。脑部疾病,尤其是缺血性中风,癫痫,和创伤性脑损伤，引发离子梯度失调，促进神经递质和锌的过度释放。二价金属阳离子锌在脑中高度分布，并作为自由离子特别位于突触前囊泡中，通常存在于与金属硫蛋白结合的细胞质中。尽管充足的锌对于调节多种生理功能至关重要，脑部疾病引起的锌的过度释放和移位会导致细胞损伤，包括氧化应激,凋亡级联，和能量代谢紊乱。因此,脑疾病后锌稳态的调节对于预防脑损伤至关重要。在这次审查中,我们总结了最近关于TRP通道（主要是TRPC和TRPM）和锌在全脑缺血动物脑疾病模型中如何调节的实验研究结果，癫痫,和创伤性脑损伤。使用已知的通道拮抗剂通过抑制TRPC和TRPM通道阻断锌转运，被证明对脑部疾病具有神经保护作用。锌和TRP通道的调节可以作为治疗和预防神经元死亡的靶标。
