Macdonald W A, Ørtenblad N, Nielsen O B
Institute of Physiology and Biophysics, University of Aarhus, DK-8000, Aarhus C, Denmark.
Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E771-8. doi: 10.1152/ajpendo.00378.2006. Epub 2006 Nov 7.
High-frequency stimulation of skeletal muscle has long been associated with ionic perturbations, resulting in the loss of membrane excitability, which may prevent action potential propagation and result in skeletal muscle fatigue. Associated with intense skeletal muscle contractions are large changes in muscle metabolites. However, the role of metabolites in the loss of muscle excitability is not clear. The metabolic state of isolated rat extensor digitorum longus muscles at 30 degrees C was manipulated by decreasing energy expenditure and thereby allowed investigation of the effects of energy conservation on skeletal muscle excitability. Muscle ATP utilization was reduced using a combination of the cross-bridge cycling blocker N-benzyl-p-toluene sulfonamide (BTS) and the SR Ca2+ release channel blocker Na-dantrolene, which reduce activity of the myosin ATPase and SR Ca2+-ATPase. Compared with control muscles, the resting metabolites ATP, phosphocreatine, creatine, and lactate, as well as the resting muscle excitability as measured by M-waves, were unaffected by treatment with BTS plus dantrolene. Following 20 or 30 s of continuous 60-Hz stimulation, BTS-plus-dantrolene-treated muscles showed a 25% lower ATP utilization compared with control muscles. Furthermore, the ability of muscles to maintain excitability during high-frequency stimulation was significantly improved in BTS-plus-dantrolene-treated muscles, indicating a strong link between metabolites, energetic state, and the excitability of the muscle.
长期以来，骨骼肌的高频刺激一直与离子紊乱有关，导致膜兴奋性丧失，这可能会阻止动作电位的传播并导致骨骼肌疲劳。与强烈的骨骼肌收缩相关的是肌肉代谢物的巨大变化。然而，代谢物在肌肉兴奋性丧失中的作用尚不清楚。通过减少能量消耗来控制30℃下分离的大鼠趾长伸肌的代谢状态，从而研究能量守恒对骨骼肌兴奋性的影响。使用跨桥循环阻滞剂N-苄基对甲苯磺酰胺（BTS）和SR Ca2+释放通道阻滞剂丹曲林的组合来降低肌肉ATP的利用，这两种药物可降低肌球蛋白ATP酶和SR Ca2+-ATP酶的活性。与对照肌肉相比，静息代谢物ATP、磷酸肌酸、肌酸和乳酸，以及通过M波测量的静息肌肉兴奋性，均不受BTS加丹曲林处理的影响。在连续60Hz刺激20或30秒后，与对照肌肉相比，BTS加丹曲林处理的肌肉的ATP利用率降低了25%。此外，在BTS加丹曲林处理的肌肉中，肌肉在高频刺激期间维持兴奋性的能力显著提高，这表明代谢物、能量状态和肌肉兴奋性之间存在紧密联系。
