Department of Physiology and Biophysics, University of Aarhus, DK-8000 C, Denmark.
J Physiol. 2010 Dec 1;588(Pt 23):4785-94. doi: 10.1113/jphysiol.2010.196568. Epub 2010 Sep 27.
Studies on rats have shown that lactic acid can improve excitability and function of depolarized muscles. The effect has been related to the ensuing reduction in intracellular pH causing inhibition of muscle fibre Cl(-) channels. However, since several carboxylic acids with structural similarities to lactate can inhibit muscle Cl(-) channels it is possible that lactate per se can increase muscle excitability by exerting a direct effect on these channels. We therefore examined the effects of lactate on the function of intact muscles and skinned fibres together with effects on pH and Cl(-) conductance (G(cl)). In muscles where extracellular compound action potentials (M-waves) and tetanic force response to excitation were reduced by (mean ± s.e.m.) 82 ± 4% and 83 ± 2%, respectively, by depolarization with 11 mm extracellular K(+), both M-waves and force exhibited an up to 4-fold increase when 20 mm lactate was added. This effect was present already at 5 mm and saturated at 15 mm lactate, and was associated with a 31% reduction in G(Cl). The effects of lactate were completely blocked by Cl(-) channel inhibition or use of Cl(-)-free solutions. Finally, both experiments where effects of lactate on intracellular pH in intact muscles were mimicked by increased CO₂ tension and experiments with skinned fibres showed that the effects of lactate could not be related to reduced intracellular pH. It is concluded that addition of lactate can inhibit ClC-1 Cl(-) channels and increase the excitability and contractile function of depolarized rat muscles via mechanisms not related to a reduction in intracellular pH.
研究表明，乳酸可以提高去极化肌肉的兴奋性和功能。这种作用与随后的细胞内 pH 值降低有关，导致肌肉纤维氯离子通道抑制。然而，由于乳酸与结构相似的几种羧酸可以抑制肌肉氯离子通道，因此乳酸本身可能通过对这些通道产生直接影响来增加肌肉兴奋性。因此，我们检查了乳酸对完整肌肉和去皮纤维功能的影响，以及对 pH 值和氯离子电导 (G(cl)) 的影响。在肌肉中，当用 11 mM 细胞外钾使细胞外复合动作电位 (M 波) 和兴奋时的强直力反应分别降低 82 ± 4%和 83 ± 2%时，当添加 20 mM 乳酸时，M 波和力分别增加了 4 倍。这种效应在 5 mM 时已经存在，在 15 mM 乳酸时达到饱和，并且与氯离子电导 (G(cl)) 减少 31%有关。乳酸的作用被氯离子通道抑制或使用无氯离子溶液完全阻断。最后，通过增加 CO₂张力模拟乳酸对完整肌肉细胞内 pH 值的影响的实验以及使用去皮纤维的实验表明，乳酸的作用不能与细胞内 pH 值降低有关。结论是，添加乳酸可以抑制 ClC-1 氯离子通道，并通过与降低细胞内 pH 值无关的机制增加去极化大鼠肌肉的兴奋性和收缩功能。
