Putative calcium-binding domains of the Caenorhabditis elegans BK channel are dispensable for intoxication and ethanol activation.
Putative calcium-binding domains of the Caenorhabditis elegans BK channel are dispensable for intoxication and ethanol activation.
复制标题
假定的秀丽隐杆线虫 BK 通道的钙结合域对于中毒和乙醇激活是可有可无的。
DOI：
10.1111/gbb.12229
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Pierce-Shimomura,JT
中科院分区：
文献类型：
--
作者：
Davis,SJ;Scott,LL;Ordemann,G;Philpo,A;Cohn,J;Pierce-Shimomura,JT
Alcohol modulates the highly conserved, voltage‐ and calcium‐activated potassium (BK) channel, which contributes to alcohol‐mediated behaviors in species from worms to humans. Previous studies have shown that the calcium‐sensitive domains, RCK1 and the Ca2+bowl, are required for ethanol activation of the mammalian BK channelin vitro. In the nematodeCaenorhabditis elegans, ethanol activates the BK channelin vivo, and deletion of the worm BK channel, SLO‐1, confers strong resistance to intoxication. To determine if the conserved RCK1 and calcium bowl domains were also critical for intoxication and basal BK channel‐dependent behaviors inC. elegans, we generated transgenic worms that express mutated SLO‐1 channels predicted to have the RCK1, Ca2+bowl or both domains rendered insensitive to calcium. As expected, mutating these domains inhibited basal function of SLO‐1in vivoas neck and body curvature of these mutants mimicked that of the BK null mutant. Unexpectedly, however, mutating these domains singly or together in SLO‐1 had no effect on intoxication inC. elegans. Consistent with these behavioral results, we found that ethanol activated the SLO‐1 channelin vitrowith or without these domains. By contrast, in agreement with previousin vitrofindings,C. elegansharboring a human BK channel with mutated calcium‐sensing domains displayed resistance to intoxication. Thus, for the worm SLO‐1 channel, the putative calcium‐sensitive domains are critical for basalin vivofunction but unnecessary forin vivoethanol action.
