Reduced resting potentials in dystrophic (mdx) muscle fibers are secondary to NF-κB-dependent negative modulation of ouabain sensitive Na+-K+ pump activity.
Reduced resting potentials in dystrophic (mdx) muscle fibers are secondary to NF-κB-dependent negative modulation of ouabain sensitive Na+-K+ pump activity.
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DOI：
10.1016/j.jns.2011.01.015
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发表时间：
2011-04-15
影响因子：
4.4
通讯作者：
Carlson, C. G.
中科院分区：
文献类型：
--
作者：
Miles, M. T.;Cottey, E.;Cottey, A.;Stefanski, C.;Carlson, C. G.
关键词：
为了研究成熟营养不良（mdx）肌纤维的静息膜电位（RP）降低的潜在机制，将Na+ - K+泵抑制剂哇巴因加入到新鲜分离的非营养不良和mdx纤维中。哇巴因在mdx纤维中产生的去极化比在非营养不良纤维中小71%，使非营养不良纤维中的[Na+]i增加40%，但对mdx纤维的[Na+]i没有显著影响，这大约是在未处理的非营养不良纤维中观察到的两倍。蛋白质印迹显示非营养不良和mdx肌肉之间总的和磷酸化的Na+ - K+ ATP酶催化α1亚基没有差异。NF-κB抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）的作用检查表明，直接应用药物缓慢超极化mdx纤维（90分钟内7 mV），但对非营养不良纤维没有影响。哇巴因预处理消除了这种超极化，PDTC预处理恢复了哇巴因诱导的去极化，并降低了[Na+]i。给予NF-κB抑制剂熊去氧胆酸（UDCA），该抑制剂利用不同的机制降低核NF-κB活化，也是超极化的mdx纤维。这些结果表明，NF-κB依赖性调节剂抑制了成熟营养不良纤维中的原位Na+ - K+泵活性，并且这种泵活性的降低导致了营养不良肌肉的虚弱特征。
To examine potential mechanisms for the reduced resting membrane potentials (RP) of mature dystrophic (mdx) muscle fibers, the Na+ - K+ pump inhibitor ouabain was added to freshly isolated nondystrophic and mdx fibers. Ouabain produced a 71% smaller depolarization in mdx fibers than in nondystrophic fibers, increased the [Na+]i in nondystrophic fibers by 40%, but had no significant effect on the [Na+]i of mdx fibers, which was approximately double that observed in untreated nondystrophic fibers. Western blots indicated no difference in total and phosphorylated Na+ - K+ ATPase catalytic α1 subunit between nondystrophic and mdx muscle Examination of the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) indicated that direct application of the drug slowly hyperpolarized mdx fibers (7 mV in 90 minutes) but had no effect on nondystrophic fibers. Pretreatment with ouabain abolished this hyperpolarization, and pretreatment with PDTC restored ouabain-induced depolarization and reduced [Na+]i Administration of an NF-κB inhibitor that utilizes a different mechanism for reducing nuclear NF-κB activation, ursodeoxycholic acid (UDCA), also hyperpolarized mdx fibers. These results suggest that in situ Na+ - K+ pump activity is depressed in mature dystrophic fibers by NF-κB dependent modulators, and that this reduced pump activity contributes to the weakness characteristic of dystrophic muscle.
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DOI：
10.1046/j.1365-201x.1996.201000.x
发表时间：
1996-03-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
Gillis, JM
通讯作者：
Gillis, JM
影响因子：
3.3
作者：
Féraille, E;Carranza, ML;Favre, H
通讯作者：
Favre, H
影响因子：
4.4
作者：
KURIHARA, T;KISHI, M;KINOSHITA, M
通讯作者：
KINOSHITA, M
影响因子：
5.5
作者：
De Backer, F;Vandebrouck, C;Gillis, JM
通讯作者：
Gillis, JM
影响因子：
6.1
作者：
Carlson, CG;Samadi, A;Siegel, A
通讯作者：
Siegel, A