TMC Proteins Modulate Membrane Excitability through a Background Na+ Conductance

发布日期:2018-03-27

 

时   间:   2018年3月27日? 12:20-13:20

地  点:   清华大学医学科学楼B323

讲座嘉宾:康利军教授

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主持人:欧光朔,清华-IDG/麦戈文脑科学研究院研究员

题目:TMC Proteins Modulate Membrane Excitability through a Background Na+ Conductance.

摘要:How Membrane excitability is a fundamentally important feature for all excitable cells including both neurons and muscle cells. However, the background depolarizing conductances in excitable cells, especially in muscle cells, are not well characterized. Although mutations in transmembrane channel-like (TMC) proteins TMC1 and TMC2 cause deafness and vestibular defects in mammals, their precise action modes are elusive. Here, we discover that both TMC-1 and TMC-2 are required for normal egg laying in C. elegans. Mutations in these TMC proteins cause membrane hyperpolarization and disrupt the rhythmic calcium activities in both neurons and muscles involved in egg laying. Mechanistically, TMC proteins enhance membrane depolarization through background leak currents and ectopic expression of both C. elegans and mammalian TMC proteins results in membrane depolarization. Therefore, we have identified an unexpected role of TMC proteins in modulating membrane excitability. Our results may provide mechanistic insights into the functions of TMC proteins in hearing loss and other diseases.