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Pharmacological profiling of stretch activated channels in proprioceptive neurons.
Comparative Biochemistry and Physiology C: Toxicology & Pharmacology ( IF 3.9 ) Pub Date : 2020-04-17 , DOI: 10.1016/j.cbpc.2020.108765
Shelby McCubbin 1 , Anna Jeoung 1 , Courtney Waterbury 1 , Robin L Cooper 1
Affiliation  

Proprioception in mammals and invertebrates occurs through stretch activated ion channels (SACs) localized in sensory endings. In mammals, the primary organs for proprioception are the intrafusal muscle spindles embedded within extrafusal muscle. In invertebrates there are varied types of sensory organs, from chordotonal organs spanning joints to muscle receptor organs (MRO) which are analogous to the mammalian muscle spindles that monitor stretch of muscle fibers. A subset of SACs are the PIEZO channels. They are comprised of a distinct type of protein sequence and are similar among species, from mammals to invertebrates. We screened several new agents (YODA 1, JEDI 2, OB 1 and DOOKU) which have been identified to act on SACs of the PIEZO 1 subtype. JEDI 2 increased activity in the crayfish MRO but not the crab chordotonal organs. The SACs of the crustacean proprioceptors have not been satisfactorily pharmacologically classified, nor has their molecular makeup been identified. We screened these pharmacological agents on model sensory organs in crustaceans to learn more about their subtype classification and compare genomic profiles of related species.

中文翻译:

本体感受神经元中拉伸激活通道的药理学分析。

哺乳动物和无脊椎动物中的本体感受是通过位于感觉末端的拉伸激活离子通道(SAC)发生的。在哺乳动物中,本体感受的主要器官是嵌在融合神经外肌肉中的融合神经内肌纺锤体。在无脊椎动物中,感觉器官的类型各不相同,从跨关节的弦状器官到肌肉受体器官(MRO),类似于监视肌肉纤维伸展的哺乳动物肌肉纺锤体。SAC的一个子集是PIEZO通道。它们由不同类型的蛋白质序列组成,并且在物种之间(从哺乳动物到无脊椎动物)相似。我们筛选了几种新的活性剂(YODA 1,JEDI 2,OB 1和DOOKU),它们已被确定可作用于PIEZO 1亚型的SAC。JEDI 2增加了小龙虾MRO中的活性,但不增加蟹的软骨器官。甲壳类本体感受器的SAC尚未令人满意地进行药理分类,也未鉴定其分子组成。我们在甲壳动物的模型感觉器官中筛选了这些药理剂,以了解有关其亚型分类的更多信息并比较相关物种的基因组概况。
更新日期:2020-04-21
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