Cairns Simeon P, Leader John P, Loiselle Denis S, Higgins Amanda, Lin Wei, Renaud Jean-Marc
Sports Performance Research Institute New Zealand, School of Sport and Recreation, Faculty of Health and Environmental Sciences, AUT University, Auckland, New Zealand; Health and Rehabilitation Research Institute, Faculty of Health and Environmental Sciences, AUT University, Auckland, New Zealand;
Department of Medicine, University of Otago, Dunedin, New Zealand; Department of Physiology, University of Otago, Dunedin, New Zealand;
J Appl Physiol (1985). 2015 Mar 15;118(6):662-74. doi: 10.1152/japplphysiol.00705.2013. Epub 2015 Jan 8.
We examined whether a Ca(2+)-K(+) interaction was a potential mechanism operating during fatigue with repeated tetani in isolated mouse muscles. Raising the extracellular Ca(2+) concentration ([Ca(2+)]o) from 1.3 to 10 mM in K(+)-depressed slow-twitch soleus and/or fast-twitch extensor digitorum longus muscles caused the following: 1) increase of intracellular K(+) activity by 20-60 mM (raised intracellular K(+) content, unchanged intracellular fluid volume), so that the K(+)-equilibrium potential increased by ∼10 mV and resting membrane potential repolarized by 5-10 mV; 2) large restoration of action potential amplitude (16-54 mV); 3) considerable recovery of excitable fibers (∼50% total); and 4) restoration of peak force with the peak tetanic force-extracellular K(+) concentration ([K(+)]o) relationship shifting rightward toward higher [K(+)]o. Double-sigmoid curve-fitting to fatigue profiles (125 Hz for 500 ms, every second for 100 s) showed that prior exposure to raised [K(+)]o (7 mM) increased, whereas lowered [K(+)]o (2 mM) decreased, the rate and extent of force loss during the late phase of fatigue (second sigmoid) in soleus, hence implying a K(+) dependence for late fatigue. Prior exposure to 10 mM [Ca(2+)]o slowed late fatigue in both muscle types, but was without effect on the extent of fatigue. These combined findings support our notion that a Ca(2+)-K(+) interaction is plausible during severe fatigue in both muscle types. We speculate that a diminished transsarcolemmal K(+) gradient and lowered [Ca(2+)]o contribute to late fatigue through reduced action potential amplitude and excitability. The raised [Ca(2+)]o-induced slowing of fatigue is likely to be mediated by a higher intracellular K(+) activity, which prolongs the time before stimulation-induced K(+) efflux depolarizes the sarcolemma sufficiently to interfere with action potentials.
我们研究了在离体小鼠肌肉中，重复强直刺激导致疲劳的过程中，Ca(2+)-K(+)相互作用是否是一种潜在的作用机制。在低钾抑制的慢肌比目鱼肌和/或快肌趾长伸肌中，将细胞外Ca(2+)浓度（[Ca(2+)]o）从1.3 mM提高到10 mM会产生以下结果：1）细胞内K(+)活性增加20 - 60 mM（细胞内K(+)含量升高，细胞内液体积不变），使得K(+)平衡电位增加约10 mV，静息膜电位复极化5 - 10 mV；2）动作电位幅度大幅恢复（16 - 54 mV）；3）可兴奋纤维显著恢复（约占总数的50%）；4）峰值力恢复，强直收缩峰值力-细胞外K(+)浓度（[K(+)]o）关系向右移向更高的[K(+)]o。对疲劳曲线（125 Hz，持续500 ms，每秒一次，共100 s）进行双S形曲线拟合表明，预先暴露于升高的[K(+)]o（7 mM）会增加比目鱼肌疲劳后期（第二个S形）力损失的速率和程度，而降低的[K(+)]o（2 mM）则会降低，这意味着后期疲劳存在K(+)依赖性。预先暴露于10 mM [Ca(2+)]o会减缓两种肌肉类型的后期疲劳，但对疲劳程度没有影响。这些综合发现支持了我们的观点，即在两种肌肉类型的严重疲劳过程中，Ca(2+)-K(+)相互作用是合理的。我们推测，跨肌膜K(+)梯度减小和[Ca(2+)]o降低通过降低动作电位幅度和兴奋性导致后期疲劳。升高的[Ca(2+)]o诱导的疲劳减缓可能是由较高的细胞内K(+)活性介导的，这延长了刺激诱导的K(+)外流使肌膜充分去极化以干扰动作电位之前的时间。
