Halliwell Robert F
Schools of Pharmacy & Dentistry, University of the Pacific, 751 Brookside Road, Stockton, CA, USA.
Neurochem Int. 2017 Jun;106:37-47. doi: 10.1016/j.neuint.2016.10.003. Epub 2016 Oct 11.
Functional studies of neurons have traditionally used nervous system tissues from a variety of non-human vertebrate and invertebrate species, even when the focus of much of this research has been directed at understanding human brain function. Over the last decade, the identification and isolation of human stem cells from embryonic, tissue (or adult) and induced pluripotent stem cells (iPSCs) has revolutionized the availability of human neurons for experimental studies in vitro. In addition, the direct conversion of terminally differentiated fibroblasts into Induced neurons (iN) has generated great excitement because of the likely value of such human stem cell derived neurons (hSCNs) and iN cells in drug discovery, neuropharmacology, neurotoxicology and regenerative medicine. This review addresses the current state of our knowledge of functional receptors and ion channels expressed in neurons derived from human stem cells and iNeurons and identifies gaps and questions that might be investigated in future studies; it focusses almost exclusively on what is known about the electrophysiological properties of neurons derived from human stem cells and iN cells in vitro with an emphasis on voltage and ligand gated ion channels, since these mediate synaptic signalling in the nervous system and they are at the heart of neuropharmacology.
传统上,神经元的功能研究使用来自各种非人类脊椎动物和无脊椎动物物种的神经系统组织,即便大部分此类研究的重点是理解人类大脑功能。在过去十年中,从胚胎、组织(或成体)干细胞以及诱导多能干细胞(iPSC)中鉴定和分离人类干细胞,彻底改变了用于体外实验研究的人类神经元的可获得性。此外,终末分化的成纤维细胞直接转化为诱导神经元(iN)引发了极大的关注,因为这类源自人类干细胞的神经元(hSCN)和iN细胞在药物发现、神经药理学、神经毒理学和再生医学中可能具有重要价值。本综述阐述了我们目前对源自人类干细胞和诱导神经元的神经元中表达的功能性受体和离子通道的了解状况,并指出了未来研究中可能有待探讨的空白和问题;它几乎完全聚焦于对源自人类干细胞和iN细胞的神经元在体外的电生理特性的已知情况,重点是电压门控离子通道和配体门控离子通道,因为这些通道介导神经系统中的突触信号传递,且是神经药理学的核心所在。