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从能量储存到能量通量:对肌酸激酶缺陷型快肌骨骼肌的一项研究。

From energy store to energy flux: a study in creatine kinase-deficient fast skeletal muscle.

作者信息

Kaasik Allen, Veksler Vladimir, Boehm Ernest, Novotova Marta, Ventura-Clapier Renée

机构信息

U-446 INSERM, Université Paris-Sud, 92296 Châtenay-Malabry, France.

出版信息

FASEB J. 2003 Apr;17(6):708-10. doi: 10.1096/fj.02-0684fje. Epub 2003 Feb 5.

Abstract

Fast-twitch skeletal muscle of mice deficient in cytosolic and mitochondrial creatine kinase isoforms (CK-/-) lack burst activity but can sustain prolonged contractile activity, suggesting that adaptive mechanisms can regulate local adenine nucleotide turnover. We investigated whether direct energy and signal channeling between mitochondria and sarcoplasmic reticulum (SR) or myofilaments may exist that compensate for the lack of CK isoenzymes. Oxidative capacity of fast-twitch muscle was increased twofold in CK-/- mice. Energy cross talk between organelles was studied in muscle fibers with permeabilized sarcolemma. Energy supply to SR was estimated by analyzing the tension transient induced by caffeine and energy supply to myofilaments was estimated by the relaxation of rigor tension, both under different conditions of energy supply. In normal mice, ATP directly produced by mitochondria was not able to sustain calcium uptake and to relax rigor tension as efficiently as ATP produced by bound CK. However, in CK-/- mice, mitochondria ability to provide ATP for calcium uptake and relaxation of rigor tension was dramatically enhanced, suggesting a direct ATP/ADP channeling between sites of energy production mitochondria) and energy utilization in CK-/- mice. These results demonstrate two possible patterns of energy transport in muscle cells: energy store with phosphocreatine and energy flux through mitochondria.

摘要

缺乏胞质和线粒体肌酸激酶同工型(CK-/-)的小鼠快肌骨骼肌缺乏爆发性活动,但能维持长时间的收缩活动,这表明适应性机制可调节局部腺嘌呤核苷酸周转。我们研究了线粒体与肌浆网(SR)或肌丝之间是否存在直接的能量和信号传递,以弥补CK同工酶的缺失。CK-/-小鼠快肌的氧化能力提高了两倍。在肌膜通透的肌纤维中研究了细胞器之间的能量相互作用。在不同能量供应条件下,通过分析咖啡因诱导的张力瞬变来估计向SR的能量供应,通过强直张力的松弛来估计向肌丝的能量供应。在正常小鼠中,线粒体直接产生的ATP不能像结合型CK产生的ATP那样有效地维持钙摄取和松弛强直张力。然而,在CK-/-小鼠中,线粒体为钙摄取和松弛强直张力提供ATP的能力显著增强,这表明在CK-/-小鼠中能量产生部位(线粒体)与能量利用部位之间存在直接的ATP/ADP传递。这些结果证明了肌肉细胞中两种可能的能量运输模式:磷酸肌酸的能量储存和通过线粒体的能量通量。

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