Westerblad H, Allen D G
Department of Physiology, University of Sydney, New South Wales, Australia.
J Gen Physiol. 1991 Sep;98(3):615-35. doi: 10.1085/jgp.98.3.615.
Measurements of the intracellular free concentration of Ca2+ ([Ca2+]i) were performed during fatiguing stimulation of intact, single muscle fibers, which were dissected from a mouse foot muscle and loaded with fura-2. Fatigue, which was produced by repeated 100-Hz tetani, generally occurred in three phases. Initially, tension declined rapidly to approximately 90% of the original tension (0.9 Po) and during this period the tetanic [Ca2+]i increased significantly (phase 1). Then followed a lengthy period of almost stable tension production and tetanic [Ca2+]i (phase 2). Finally, both the tetanic [Ca2+]i and tension fell relatively fast (phase 3). The resting [Ca2+]i rose continuously throughout the stimulation period. A 10-s rest period during phase 3 resulted in a significant increase of both tetanic [Ca2+]i and tension, whereas a 10-s pause during phase 2 did not have any marked effect. Application of caffeine under control conditions and early during phase 2 resulted in a substantial increase of the tetanic [Ca2+]i but no marked tension increase, whereas caffeine applied at the end of fatiguing stimulation (tension depressed to approximately 0.3 Po) gave a marked increase of both tetanic [Ca2+]i and tension. The tetanic [Ca2+]i for a given tension was generally higher during fatiguing stimulation than under control conditions. Fatigue developed more rapidly in fibers exposed to cyanide. In these fibers there was no increase of tetanic [Ca2+]i during phase 1 and the increase of the resting [Ca2+]i during fatiguing stimulation was markedly larger. The present results indicate that fatigue produced by repeated tetani is caused by a combination of reduced maximum tension-generating capacity, reduced myofibrillar Ca2+ sensitivity, and reduced Ca2+ release from the sarcoplasmic reticulum. The depression of maximum tension-generating capacity develops early during fatiguing stimulation and it is of greatest importance for the force decline at early stages of fatigue. As fatigue gets more severe, reduced Ca2+ sensitivity and reduced Ca2+ release become quantitatively more important for the tension decline.
在对完整的单根肌纤维进行疲劳刺激期间，测量细胞内游离钙离子浓度（[Ca2+]i）。这些肌纤维取自小鼠足部肌肉，用fura - 2进行负载。由100Hz重复强直刺激产生的疲劳通常分为三个阶段。最初，张力迅速下降至约为原始张力的90%（0.9Po），在此期间强直[Ca2+]i显著增加（第1阶段）。接着是一段较长时间的几乎稳定的张力产生和强直[Ca2+]i阶段（第2阶段）。最后，强直[Ca2+]i和张力都相对快速下降（第3阶段）。静息[Ca2+]i在整个刺激期间持续上升。在第3阶段的10秒休息期导致强直[Ca2+]i和张力都显著增加，而在第2阶段的10秒暂停没有任何明显影响。在对照条件下以及在第2阶段早期应用咖啡因会导致强直[Ca2+]i大幅增加，但张力没有明显增加，而在疲劳刺激结束时（张力降至约0.3Po）应用咖啡因会使强直[Ca2+]i和张力都显著增加。在疲劳刺激期间，给定张力下的强直[Ca2+]i通常高于对照条件下。在暴露于氰化物的纤维中疲劳发展得更快。在这些纤维中，第1阶段强直[Ca2+]i没有增加，并且在疲劳刺激期间静息[Ca2+]i的增加明显更大。目前的结果表明，重复强直刺激产生的疲劳是由最大张力产生能力降低、肌原纤维Ca2+敏感性降低以及肌浆网Ca2+释放减少共同引起的。最大张力产生能力的降低在疲劳刺激早期就出现，并且对于疲劳早期阶段的力下降最为重要。随着疲劳变得更严重，Ca2+敏感性降低和Ca2+释放减少对于张力下降在数量上变得更加重要。
