Excitability properties of mouse and human skeletal muscle fibres compared by muscle velocity recovery cycles.
Excitability properties of mouse and human skeletal muscle fibres compared by muscle velocity recovery cycles.
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DOI：
10.1016/j.nmd.2022.02.011
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Tan SV
中科院分区：
文献类型：
--
作者：
Suetterlin KJ;Männikkö R;Matthews E;Greensmith L;Hanna MG;Bostock H;Tan SV
骨骼肌通道病的小鼠模型并不是人类疾病的表型。在某些情况下(例如，先天性肌强直)，表型要严重得多，而在其他情况下(例如，低血钾性周期性麻痹)，啮齿动物的生理是保护性的。这表明了不同物种在肌肉兴奋性特性上的差异。在人类中，这些可以通过肌肉速度恢复周期(MVRC)，通过脉冲后传导速度的变化来间接测量。我们在小鼠身上进行了MVRC实验，并将它们的肌肉兴奋性特性与人类进行了比较。小鼠胫前肌MVRCs(n=70)只有一个异常时相(传导速度增快)，其幅度较小(p=9×10-21)，持续时间(p=3×10-24)较人(n=26)短。这种短暂的异常之后是小鼠的晚期亚正常(速度减慢)，在时间上与在人类MVRC中看到的晚期异常重叠。晚期异常期提示T小管Na+/K+泵活性升高。通过阻断氯离子通道，小鼠的非正常时相转变为异常，提示小鼠的氯离子电导相对较高。我们的发现有助于解释患有骨骼肌通道病和潜在的其他神经肌肉疾病的小鼠和人类在表型上的差异。MVRCs是一种有价值的新工具，用于比较不同物种之间的活体肌膜特性，并将允许进一步剖析调节肌肉兴奋性的分子机制。
Mouse models of skeletal muscle channelopathies are not phenocopies of human disease. In some cases (e.g., Myotonia Congenita) the phenotype is much more severe, whilst in others (e.g. Hypokalaemic periodic paralysis) rodent physiology is protective. This suggests a species’ difference in muscle excitability properties. In humans these can be measured indirectly by the post-impulse changes in conduction velocity, using Muscle Velocity Recovery Cycles (MVRCs). We performed MVRCs in mice and compared their muscle excitability properties with humans. Mouse Tibialis Anterior MVRCs (n=70) have only one phase of supernormality (increased conduction velocity), which is smaller in magnitude (p=9×10-21), and shorter in duration (p=3×10-24) than human (n=26). This abbreviated supernormality is followed by a period of late subnormality (reduced velocity) in mice, which overlaps in time with the late supernormality seen in human MVRCs. The period of late subnormality suggests increased t-tubule Na+/K+-pump activity. The subnormal phase in mice was converted to supernormality by blocking chloride channels, suggesting relatively higher chloride conductance in mouse. Our findings help explain discrepancies in phenotype between mice and humans with skeletal muscle channelopathies and potentially other neuromuscular disorders. MVRCs are a valuable new tool to compare in vivo muscle membrane properties between species and will allow further dissection of the molecular mechanisms regulating muscle excitability.
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NAV1.4营养不良骨骼肌的放松管制导致NA+超负荷并增强细胞死亡。
影响因子：
3.8
作者：
Hirn, Carole;Shapovalov, George;Petermann, Olivier;Roulet, Emmanuelle;Ruegg, Urs T.
通讯作者：
Ruegg, Urs T.
影响因子：
4.7
作者：
Desaphy JF;Costanza T;Carbonara R;Conte Camerino D
通讯作者：
Conte Camerino D
影响因子：
15.9
作者：
Hayward, Lawrence J.;Kim, Joanna S.;Brown, Robert H., Jr.
通讯作者：
Brown, Robert H., Jr.
影响因子：
5.5
作者：
Call, Jarrod A.;Warren, Gordon L.;Lowe, Dawn A.
通讯作者：
Lowe, Dawn A.
影响因子：
2.5
作者：
FRANK, GB
通讯作者：
FRANK, GB