Progress in automating patch clamp cellular physiology.
Progress in automating patch clamp cellular physiology.
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DOI：
10.1177/2398212818776561
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Schultz, Simon R
中科院分区：
文献类型：
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作者：
Annecchino, Luca A;Schultz, Simon R
在过去的几十年里，膜片钳电生理学已经改变了生命科学的研究。自问世以来，自动膜片钳平台已经有了很大的发展，证明了解决电压和配体门控通道的能力，并显示出在药物发现和生物医学研究中发挥关键作用的潜力。不幸的是，早期系统所局限的细胞悬液试验不能重建生物相关的细胞环境，也不能捕捉突触生理学和网络动力学的更高阶方面。体内膜片钳电生理学有可能产生更多的生物复杂信息，在单细胞和网络神经元计算的分子和细胞机制的逆向工程中特别有用，同时捕获人类疾病机制和可能的治疗策略的重要方面。不幸的是，这是一个困难的过程，学习曲线陡峭，这限制了技术的传播。幸运的是，体内膜片钳电生理似乎特别适合机器人自动化。在这篇综述中，我们记录了自动化膜片钳技术的发展，从早期基于多孔板的系统到自动化平面阵列平台，以及能够在体内进行双光子靶向全细胞电生理记录的现代机器人平台。
Patch clamp electrophysiology has transformed research in the life sciences over the last few decades. Since their inception, automatic patch clamp platforms have evolved considerably, demonstrating the capability to address both voltage- and ligand-gated channels, and showing the potential to play a pivotal role in drug discovery and biomedical research. Unfortunately, the cell suspension assays to which early systems were limited cannot recreate biologically relevant cellular environments, or capture higher order aspects of synaptic physiology and network dynamics. In vivo patch clamp electrophysiology has the potential to yield more biologically complex information and be especially useful in reverse engineering the molecular and cellular mechanisms of single-cell and network neuronal computation, while capturing important aspects of human disease mechanisms and possible therapeutic strategies. Unfortunately, it is a difficult procedure with a steep learning curve, which has restricted dissemination of the technique. Luckily, in vivo patch clamp electrophysiology seems particularly amenable to robotic automation. In this review, we document the development of automated patch clamp technology, from early systems based on multi-well plates through to automated planar-array platforms, and modern robotic platforms capable of performing two-photon targeted whole-cell electrophysiological recordings in vivo.