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标题：Evidence for redox sensing by a human cardiac calcium channel
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作者：Padmapriya Muralidharan ; Henrietta Cserne Szappanos ; Evan Ingley 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
DOI：10.1038/srep19067
出版社：Springer Nature
摘要：Ion channels are critical to life and respond rapidly to stimuli to evoke physiological responses. Calcium influx into heart muscle occurs through the ion conducting α1C subunit (Ca_v1.2) of the L-type Ca²⁺ channel. Glutathionylation of Ca_v1.2 results in increased calcium influx and is evident in ischemic human heart. However controversy exists as to whether direct modification of Ca_v1.2 is responsible for altered function. We directly assessed the function of purified human Ca_v1.2 in proteoliposomes. Truncation of the C terminus and mutation of cysteines in the N terminal region and cytoplasmic loop III-IV linker did not alter the effects of thiol modifying agents on open probability of the channel. However mutation of cysteines in cytoplasmic loop I-II linker altered open probability and protein folding assessed by thermal shift assay. We find that C543 confers sensitivity of Ca_v1.2 to oxidative stress and is sufficient to modify channel function and posttranslational folding. Our data provide direct evidence for the calcium channel as a redox sensor that facilitates rapid physiological responses.