KATP channel deficiency in mouse flexor digitorum brevis causes fibre damage and impairs Ca2+ release and force development during fatigue in vitro
KATP channel deficiency in mouse flexor digitorum brevis causes fibre damage and impairs Ca2+ release and force development during fatigue in vitro
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DOI：
10.1113/jphysiol.2007.130955
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发表时间：
2007-07-15
影响因子：
5.5
通讯作者：
Renaud, Jean-Marc
中科院分区：
文献类型：
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作者：
Cifelli, Carlo;Bourassa, François;Renaud, Jean-Marc
K-ATP通道的激活导致更快的疲劳速率，因为通道抑制动作电位振幅，而取消通道活动在整个趾长伸肌（EDL）和比目鱼肌中没有影响。在这项研究中，我们研究了在37摄氏度的疲劳过程中，取消K-ATP通道活性的影响，细胞内游离钙（Ca-i（2+））和强直性力量使用单肌纤维和小肌束的屈趾短肌（FDB）。（i）通过将野生型肌纤维暴露于格列本脲，和（ii）使用Kir6.2基因缺失小鼠（Kir6.2（-/-）小鼠），获得K-ATP通道缺陷型肌纤维。疲劳引起的200毫秒强直收缩每秒3分钟。这项研究首次证明，废除K-ATP通道活性在37摄氏度导致更快的疲劳率，其中降低峰值Ca-i（2+）和强直力是更快的K-ATP通道缺陷的纤维比对照野生型纤维。此外，在K-ATP通道缺陷的肌纤维中也观察到几种收缩功能障碍。它们包括部分或完全超收缩的单根肌纤维，未受刺激的Ca-i（2+）和未受刺激的力的较大增加，以及较低的力恢复。我们认为，在K-ATP通道缺乏的纤维中观察到的更快的疲劳速率是因为收缩功能障碍引起的峰值Ca ~（2+）和力的降低超过了预期的较慢的降低，当通道不抑制动作电位振幅时。
Activation of the K-ATP channels results in faster fatigue rates as the channels depress action potential amplitude, whereas abolishing the channel activity has no effect in whole extensor digitorum longus (EDL) and soleus muscles. In this study, we examined the effects of abolished K-ATP channel activity during fatigue at 37 degrees C on free intracellular Ca2+ (Ca-i(2+)) and tetanic force using single muscle fibres and small muscle bundles from the flexor digitorum brevis (FDB). K-ATP channel deficient muscle fibres were obtained (i) pharmacologically by exposing wild-type fibres to glibenclamide, and (ii) genetically using null mice for the Kir6.2 gene (Kir6.2(-/-) mice). Fatigue was elicited using 200 ms tetanic contractions every second for 3 min. This study demonstrated for the first time that abolishing K-ATP channel activity at 37 degrees C resulted in faster fatigue rates, where decreases in peak Ca-i(2+) and tetanic force were faster in K-ATP channel deficient fibres than in control wild-type fibres. Furthermore, several contractile dysfunctions were also observed in K-ATP channel deficient muscle fibre. They included partially or completely supercontracted single muscle fibres, greater increases in unstimulated Ca-i(2+) and unstimulated force, and lower force recovery. We propose that the observed faster rate of fatigue in K-ATP channel deficient fibres is because the decreases in peak Ca-i(2+) and force caused by contractile dysfunctions prevail over the expected slower decreases when the channels do not depress action potential amplitude.