在秀丽隐杆线虫中，左旋咪唑抗性在单通道水平上得到了解决。
Levamisole resistance resolved at the single-channel level in Caenorhabditis elegans.
作者信息
Qian Hai, Robertson Alan P, Powell-Coffman Jo Anne, Martin Richard J
机构信息
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
出版信息
FASEB J. 2008 Sep;22(9):3247-54. doi: 10.1096/fj.08-110502. Epub 2008 Jun 2.
Abstract
Sydney Brenner promoted Caenorhabditis elegans as a model organism, and subsequent investigations pursued resistance to the nicotinic anthelmintic drug levamisole in C. elegans at a genetic level. These studies have advanced our understanding of genes associated with neuromuscular transmission and resistance to the antinematodal drug. In lev-8 and lev-1 mutant C. elegans, levamisole resistance is associated with reductions in levamisole-activated whole muscle cell currents. Although lev-8 and lev-1 are known to code for nicotinic acetylcholine receptor (nAChR) subunits, an explanation for why these currents get smaller is not available. In wild-type adults, nAChRs aggregate at neuromuscular junctions and are not accessible for single-channel recording. Here we describe a use of LEV-10 knockouts, in which aggregation is lost, to make in situ recordings of nAChR channel currents. Our observations provide an explanation for levamisole resistance produced by LEV-8 and LEV-1 mutants at the single-channel level.
摘要
悉尼·布伦纳将秀丽隐杆线虫推广为一种模式生物，随后的研究在基因层面探究了秀丽隐杆线虫对烟碱类驱虫药左旋咪唑的抗性。这些研究增进了我们对与神经肌肉传递及抗线虫药抗性相关基因的理解。在lev - 8和lev - 1突变型秀丽隐杆线虫中，左旋咪唑抗性与左旋咪唑激活的全肌细胞电流减少有关。尽管已知lev - 8和lev - 1编码烟碱型乙酰胆碱受体（nAChR）亚基，但对于为何这些电流会变小尚无解释。在野生型成虫中，nAChRs聚集在神经肌肉接头处，无法进行单通道记录。在此，我们描述了一种利用LEV - 10基因敲除品系（其中聚集现象消失）来原位记录nAChR通道电流的方法。我们的观察结果在单通道水平上解释了LEV - 8和LEV - 1突变体产生的左旋咪唑抗性。
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2
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Mol Pharmacol. 2007 May;71(5):1407-15. doi: 10.1124/mol.106.033514. Epub 2007 Feb 21.
3
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FASEB J. 2006 Dec;20(14):2606-8. doi: 10.1096/fj.06-6264fje. Epub 2006 Oct 20.
4
Identification and characterization of novel nicotinic receptor-associated proteins in Caenorhabditis elegans.秀丽隐杆线虫中新型烟碱受体相关蛋白的鉴定与表征
EMBO J. 2005 Jul 20;24(14):2566-78. doi: 10.1038/sj.emboj.7600741. Epub 2005 Jun 30.
5
Single-channel properties of N- and L-subtypes of acetylcholine receptor in Ascaris suum.猪蛔虫乙酰胆碱受体N型和L型的单通道特性
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6
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9
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