Depression of Peak Force Without Altering Calcium Sensitivity by the Superoxide Anion in Chemically Skinned Cardiac Muscle of Rat
作者:
N. MacFarlane,
D. Miller,
期刊:
Circulation Research
(OVID Available online 1992)
卷期:
Volume 70,
issue 6
页码: 1217-1224
ISSN:0009-7330
年代: 1992
出版商: OVID
关键词: free radicals;calcium sensitivity;myocardial stunning;chemically skinned muscle;force depression
数据来源: OVID
摘要:
Among the mechanisms postulated to contribute to myocardial “stunning” is a depression of contractility by oxygen-derived free radicals. It has been suggested that these radicals might depress the calcium sensitivity of the contractile proteins. We have exposed the myofilaments (in chemically “skinned” rat cardiac muscle) to the superoxide anion and measured isometric force at controlled degrees of activation. Superoxide was generated by the xanthine/xanthine oxidase system: the effects to be described were shown to be specifically attributable to superoxide. Maximum calcium-activated force is reduced, or even completely abolished, in a dose-dependent fashion and without any alteration in calcium sensitivity. The myofilaments are highly sensitive to superoxide: significant force reduction has been shown to be caused by enzyme concentrations as low as 2 microunits/ml xanthine oxidase and with exposures of less than 1 minute to the generating system (at higher enzyme concentrations). Once force has been depressed, it cannot be recovered within the duration of the experiments described. When xanthine oxidase is applied during the calcium-induced contracture, tension falls steadily. However, a similar concentration is without immediate effect on the rigor contracture (evoked by applying ATP-free solutions). To account for the depression of maximum calcium-activated force, we conclude that some aspect of crossbridge behavior is particularly vulnerable to superoxide rather than that the radical has a nonspecific “proteolytic” effect. This action on the fundamental units of force production could contribute to myocardial stunning since the effects we report are consistent with many aspects of this phenomenon.
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