Sustained overexpression of IGF-1 prevents age-dependent decrease in charge movement and intracellular Ca(2+) in mouse skeletal muscle.

Sustained overexpression of IGF-1 prevents age-dependent decrease in charge movement and intracellular Ca(2+) in mouse skeletal muscle.
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IGF-1 的持续过度表达可防止小鼠骨骼肌中电荷运动和细胞内 Ca(2) 随年龄增长而减少。

DOI:
10.1016/s0006-3495(02)75489-1
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发表时间:
2002
影响因子:
3.4
通讯作者:
Delbono,Osvaldo
Delbono,Osvaldo
中科院分区:
生物学3区
文献类型:
--
作者:
Wang,Zhong-Min;Messi,MaríaLaura;Delbono,Osvaldo

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在这项工作中,我们验证了转基因IGF-1持续过表达的假设,即阻止骨骼肌纤维中电荷运动和细胞内Ca2+的年龄依赖性减少。为此,研究了5-7月龄和21 - 24月龄FVB(野生型)和S1S2 (IGF-1转基因)小鼠的指短屈肌(FDB)肌纤维。根据描述的程序(Wang, Z. M., M. L. Messi和O. Delbono, 1999.Biophys.),以膜片钳技术的全细胞结构对纤维进行电压夹紧。j.77:2709 - 2716)。同时记录电荷运动和细胞内Ca2+浓度。幼龄野生型和转基因小鼠的最大电荷运动(Qmax)分别为(mean±SEM, in nCμF−1):52±2.1 (n=46)和54±1.9 (n=38)(无统计学意义,ns),老龄野生型和转基因小鼠的最大电荷运动(Qmax)分别为36±2.1 (n=32)和49±2.3 (n=35) (p<0.01)。幼龄野生型和转基因小鼠细胞内钙离子峰值分别为14.5±0.9和16±2.1 (ns),老龄野生型和转基因小鼠细胞内钙离子峰值分别为9.9±0.1和14±1.1 (p<0.01)。没有发现电压分布或q - vor [Ca2+]- v关系的陡峭度有明显变化。这些数据支持骨骼肌中IGF-1的过度表达可以阻止年龄依赖性电荷运动和峰值[Ca2+]i的减少。
In this work we tested the hypothesis that transgenic sustained overexpression of IGF-1 prevents age-dependent decreases in charge movement and intracellular Ca2+in skeletal muscle fibers. To this end, short flexor digitorum brevis (FDB) muscle fibers from 5–7- and 21–24-month-old FVB (wild-type) and S1S2 (IGF-1 transgenic) mice were studied. Fibers were voltage-clamped in the whole-cell configuration of the patch-clamp technique according to described procedures (Wang, Z. M., M. L. Messi, and O. Delbono. 1999.Biophys. J.77:2709–2716). Charge movement and intracellular Ca2+concentration were recorded simultaneously. The maximum charge movement (Qmax) recorded in young wild-type and transgenic mice was (mean±SEM, in nCμF−1): 52±2.1 (n=46) and 54±1.9 (n=38) (non-significant, ns), respectively, whereas in old wild-type and old transgenic mice the values were 36±2.1 (n=32) and 49±2.3 (n=35), respectively (p<0.01). The peak intracellular calcium [Ca2+]irecorded in young wild-type and transgenic mice was (inμM): 14.5±0.9 and 16±2.1 (ns), whereas in old wild-type and transgenic mice the values were 9.9±0.1 and 14±1.1 (p<0.01), respectively. No significant changes in the voltage distribution or steepness of theQ-Vor [Ca2+]-Vrelationship were found. These data support the concept that overexpression of IGF-1 in skeletal muscle prevents age-dependent reduction in charge movement and peak [Ca2+]i.