Lactic acid restores skeletal muscle force in an in vitro fatigue model: are voltage-gated chloride channels involved?
Lactic acid restores skeletal muscle force in an in vitro fatigue model: are voltage-gated chloride channels involved?
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DOI：
10.1152/ajpcell.00279.2011
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发表时间：
2012-04-01
影响因子：
5.5
通讯作者：
Iaizzo, Paul A.
中科院分区：
文献类型：
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作者：
Bandschapp, Oliver;Soule, Charles L.;Iaizzo, Paul A.
Bandschapp O，Soule CL，Iaizzo PA.乳酸在体外疲劳模型中恢复骨骼肌力量：是否涉及电压门控氯离子通道？美国生理学杂志细胞生理学302：C1019-C1025，2012年。首次发表于2012年1月11日; doi：10.1152/ajpcell.00279.2011。据报道，高间质K+浓度（[K+]）会阻碍电脉冲沿肌细胞膜（肌膜）沿着正常传播，然后进入横小管系统;这被认为是与肌肉疲劳发展相关的一种潜在机制。有趣的是，乳酸的细胞外积累，曾经被认为是肌肉疲劳的另一个原因，最近被证明在这种情况下具有恢复力量的作用。具体而言，有人提出，乳酸升高（和细胞内酸中毒）可能导致电压门控氯离子通道的抑制，从而重建更好的肌细胞肌膜的兴奋性。在本研究中，使用体外肌肉收缩实验装置，以研究功能可行的腹直肌肌肉制剂从正常猪，我们研究了20 mM乳酸和512 μ M 9-蒽羧酸（9-AC;电压门控氯离子通道阻滞剂）的K+抑制（10 mM K+）抽搐力恢复的影响。我们观察到两种治疗后相似的肌肉收缩恢复。有趣的是，在[K+]升高时，肌强直（即，过度兴奋或后去极化），通常存在于骨骼肌固有或诱导的氯离子通道功能障碍，在乳酸或9-AC存在下未观察到。在某种程度上，这些数据证实了先前的研究，表明乳酸在高[K+]条件下具有恢复力的作用。此外，我们观察到乳酸和9-AC的类似恢复作用，暗示通过电压门控氯离子通道调节的有益机制。
Bandschapp O, Soule CL, Iaizzo PA. Lactic acid restores skeletal muscle force in an in vitro fatigue model: are voltage-gated chloride channels involved?. Am J Physiol Cell Physiol 302: C1019-C1025, 2012. First published January 11, 2012; doi:10.1152/ajpcell.00279.2011.-High interstitial K+ concentration ([K+]) has been reported to impede normal propagation of electrical impulses along the muscle cell membrane (sarcolemma) and then also into the transverse tubule system; this is one considered underlying mechanism associated with the development of muscle fatigue. Interestingly, the extracellular buildup of lactic acid, once considered an additional cause for muscle fatigue, was recently shown to have force-restoring effects in such conditions. Specifically, it was proposed that elevated lactic acid (and intracellular acidosis) may lead to inhibition of voltage-gated chloride channels, thereby reestablishing better excitability of the muscle cell sarcolemma. In the present study, using an in vitro muscle contractile experimental setup to study functionally viable rectus abdominis muscle preparations obtained from normal swine, we examined the effects of 20 mM lactic acid and 512 mu M 9-anthracenecarboxylic acid (9-AC; a voltage-gated chloride channel blocker) on the force recovery of K+-depressed (10 mM K+) twitch forces. We observed a similar muscle contractile restoration after both treatments. Interestingly, at elevated [K+], myotonia (i.e., hyperexcitability or afterdepolarizations), usually present in skeletal muscle with inherent or induced chloride channel dysfunctions, was not observed in the presence of either lactic acid or 9-AC. In part, these data confirm previous studies showing a force-restoring effect of lactic acid in high-[K+] conditions. In addition, we observed similar restorative effects of lactic acid and 9-AC, implicating a beneficial mechanism via voltage-gated chloride channel modulation.