INCREASED ACTIVITY OF CALCIUM LEAK CHANNELS IN MYOTUBES OF DUCHENNE HUMAN AND MDX MOUSE ORIGIN
INCREASED ACTIVITY OF CALCIUM LEAK CHANNELS IN MYOTUBES OF DUCHENNE HUMAN AND MDX MOUSE ORIGIN
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DOI：
10.1126/science.2173137
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发表时间：
1990-11-02
期刊：
影响因子：
56.9
通讯作者：
STEINHARDT, RA
中科院分区：
文献类型：
--
作者：
FONG, P;TURNER, PR;STEINHARDT, RA
在成人营养不良肌纤维中发现的游离钙离子浓度升高会导致蛋白质降解增强。由于浓度的不同可能反映了进入的不同，正常和Duchenne人肌管以及正常和MDX鼠肌管培养物中的钙泄漏通道已经被识别和表征。在营养不良的肌管中，漏通道的开放概率显著增加。其他通道特性，如平均开放时间、单通道电导、离子选择性和在药物存在下的行为，在不同类型的肌管中是相似的。Duchenne和MDX来源的肌管细胞内静息游离钙离子浓度([Ca~(2+)]i)在Duchenne和MDX来源的肌管内首次在正常组织中表达时显著高于正常人和正常小鼠肌管内的钙离子浓度。综上所述，这些发现表明，Duchenne人和MDX小鼠肌管内游离钙浓度的升高与钙泄漏通道开放概率的增加有关。
Elevated free Ca2+ concentrations found in adult dystrophic muscle fibers result in enhanced protein degradation. Since the difference in concentrations may reflect differences in entry, Ca2+ leak channels in cultures of normal and Duchenne human myotubes, and normal and mdx murine myotubes, have been identified and characterized. The open probability of leak channels is markedly increased in dystrophic myotubes. Others channel properties, such as mean open times, single channel conductance, ion selectivity, and behavior in the presence of pharmacological agents, were similar among myotube types. Compared to the Ca2+ concentrations in normal human and normal mouse myotubes, intracellular resting free Ca2+ concentrations ([Ca2+]i) in myotubes of Duchenne and mdx origin were significantly higher at a time when dystrophin is first expressed in normal tissue. Taken together, these findings suggest that the increased open probability of Ca2+ leak channels contributes to the elevated free intracellular Ca2+ concentrations in Duchenne human and mdx mouse myotubes.