Eshima Hiroaki, Poole David C, Kano Yutaka
Department of Engineering Science, Bioscience and Technology Program, University of Electro-Communications, Chofu, Tokyo, Japan; and.
Departments of Anatomy & Physiology and Kinesiology, Kansas State University, Manhattan, Kansas.
Am J Physiol Regul Integr Comp Physiol. 2015 Jul 15;309(2):R128-37. doi: 10.1152/ajpregu.00044.2015. Epub 2015 May 6.
In Type 1 diabetes, skeletal muscle resting intracellular Ca(2+) concentration ([Ca(2+)]i) homeostasis is impaired following muscle contractions. It is unclear to what degree this behavior is contingent upon fiber type and muscle oxygenation conditions. We tested the hypotheses that: 1) the rise in resting [Ca(2+)]i evident in diabetic rat slow-twitch (type I) muscle would be exacerbated in fast-twitch (type II) muscle following contraction; and 2) these elevated [Ca(2+)]i levels would relate to derangement of microvascular partial pressure of oxygen (PmvO2 ) rather than sarcoplasmic reticulum dysfunction per se. Adult male Wistar rats were divided randomly into diabetic (DIA: streptozotocin ip) and healthy (CONT) groups. Four weeks later extensor digitorum longus (EDL, predominately type II fibers) and soleus (SOL, predominately type I fibers) muscle contractions were elicited by continuous electrical stimulation (120 s, 100 Hz). Ca(2+) imaging was achieved using fura 2-AM in vivo (i.e., circulation intact). DIA increased fatigability in EDL (P < 0.05) but not SOL. In recovery, SOL [Ca(2+)]i either returned to its resting baseline within 150 s (CONT 1.00 ± 0.02 at 600 s) or was not elevated in recovery at all (DIA 1.03 ± 0.02 at 600 s, P > 0.05). In recovery, EDL CONT [Ca(2+)]i also decreased to values not different from baseline (1.06 ± 0.01, P > 0.05) at 600 s. In marked contrast, EDL DIA [Ca(2+)]i remained elevated for the entire recovery period (i.e., 1.23 ± 0.03 at 600 s, P < 0.05). The inability of [Ca(2+)]i to return to baseline in EDL DIA was not associated with any reduction of SR Ca(2+)-ATPase (SERCA) 1 or SERCA2 protein levels (both increased 30-40%, P < 0.05). However, Pmv(O2) recovery kinetics were markedly slowed in EDL such that mean Pmv(O2) was substantially depressed (CONT 27.9 ± 2.0 vs. DIA 18.4 ± 2.0 Torr, P < 0.05), and this behavior was associated with the elevated [Ca(2+)]i. In contrast, this was not the case for SOL (P > 0.05) in that neither [Ca(2+)]i nor Pmv(O2) were deranged in recovery with DIA. In conclusion, recovery of [Ca(2+)]i homeostasis is impaired in diabetic rat fast-twitch but not slow-twitch muscle in concert with reduced Pmv(O2) pressures.
在1型糖尿病中，肌肉收缩后骨骼肌静息细胞内钙离子浓度（[Ca(2+)]i）的稳态受损。目前尚不清楚这种行为在多大程度上取决于纤维类型和肌肉氧合状况。我们检验了以下假设：1）糖尿病大鼠慢肌（I型）中静息[Ca(2+)]i的升高在收缩后的快肌（II型）中会加剧；2）这些升高的[Ca(2+)]i水平与微血管氧分压（PmvO2）的紊乱有关，而非肌浆网功能障碍本身。成年雄性Wistar大鼠随机分为糖尿病组（DIA：腹腔注射链脲佐菌素）和健康对照组（CONT）。四周后，通过连续电刺激（120秒，100赫兹）诱发趾长伸肌（EDL，主要为II型纤维）和比目鱼肌（SOL，主要为I型纤维）收缩。使用fura 2-AM在体内（即循环完整）进行Ca(2+)成像。DIA增加了EDL的疲劳性（P < 0.05），但未增加SOL的疲劳性。在恢复过程中，SOL的[Ca(2+)]i要么在150秒内恢复到静息基线（CONT在600秒时为1.00 ± 0.02），要么在恢复过程中根本没有升高（DIA在600秒时为1.03 ± 0.02，P > 0.05）。在恢复过程中，EDL CONT的[Ca(2+)]i在600秒时也降至与基线无差异的值（1.06 ± 0.01，P > 0.05）。与之形成鲜明对比的是，EDL DIA的[Ca(2+)]i在整个恢复期间都保持升高（即600秒时为1.23 ± 0.03，P < 0.05）。EDL DIA中[Ca(2+)]i无法恢复到基线与肌浆网Ca(2+)-ATP酶（SERCA）1或SERCA2蛋白水平的任何降低无关（两者均增加30 - 40%，P < 0.05）。然而，EDL中Pmv(O2)的恢复动力学明显减慢，以至于平均Pmv(O2)大幅降低（CONT为27.9 ± 2.0 vs. DIA为18.4 ± 2.0 Torr，P < 0.05），并且这种情况与升高的[Ca(2+)]i有关。相比之下，SOL并非如此（P > 0.05），因为DIA恢复过程中[Ca(2+)]i和Pmv(O2)均未紊乱。总之，糖尿病大鼠快肌而非慢肌中[Ca(2+)]i稳态的恢复受损，同时伴有Pmv(O2)压力降低。
