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[作为研究肌原纤维内肌肉收缩调节工具的鬼笔毒素]

[Phallotoxins as an instrument for studying the intramyofibrillar regulation of muscle contraction].

作者信息

Bukatina A E, Sik G S

机构信息

Department of Physiology and Biophysics, Mayo Medical School, Jo 4-184, 200 First Street SW, Rochester, MN 55905, USA.

出版信息

Biofizika. 2003 Nov-Dec;48(6):1086-93.

Abstract

The contraction of myofibrils is regulated by the coordinated action of Ca2+ and myosin cross-bridges. Phallotoxins induce a variety of specific changes in myofibrillar functioning and are therefore a potentially valuable tool for muscle research. There are two greatly differing classes of drugs among phallotoxins: (1) recently discovered secophalloidin and its derivatives. The unique property of secophalloidin is muscle activation without Ca2+, possibly by direct influence on actomyosin interaction. These drugs seem to be especially useful for studying the role of cross-bridges in muscle regulation; (2) the phalloidin group, which includes the majority of phallotoxins. When binding to the phalloidin site on F-actin, they cause muscle-specific changes. In cardiac muscle they work as Ca2+ sensitizers, increasing both the maximal force and Ca2+ sensitivity. An advantage of these drugs is that the target site is known, which allows one to unravel the sequence of molecular events leading to increased contractile function. Presumably, the complex effect of phalloidin in skeletal muscle is related to the disturbance of the actin-nebulin interaction, which may help to clarify the role of nebulin in the regulation contraction.

摘要

肌原纤维的收缩受钙离子和肌球蛋白横桥的协同作用调节。鬼笔毒素可在肌原纤维功能方面引发多种特定变化,因此是肌肉研究中一种具有潜在价值的工具。在鬼笔毒素中存在两类差异极大的药物:(1)最近发现的脱羧鬼笔环肽及其衍生物。脱羧鬼笔环肽的独特特性是在无钙离子的情况下激活肌肉,可能是通过直接影响肌动球蛋白相互作用。这些药物似乎对研究横桥在肌肉调节中的作用特别有用;(2)鬼笔环肽类,其中包括大多数鬼笔毒素。当它们与F-肌动蛋白上的鬼笔环肽位点结合时,会引起肌肉特异性变化。在心肌中,它们作为钙离子增敏剂起作用,增加最大力量和钙离子敏感性。这些药物的一个优点是其靶位点已知,这使得人们能够阐明导致收缩功能增强的分子事件序列。据推测,鬼笔环肽在骨骼肌中的复杂作用与肌动蛋白-伴肌动蛋白相互作用的紊乱有关,这可能有助于阐明伴肌动蛋白在调节收缩中的作用。

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