In vivo Ca2+ buffering capacity and microvascular oxygen pressures following muscle contractions in diabetic rat skeletal muscles: fiber-type specific effects
In vivo Ca2+ buffering capacity and microvascular oxygen pressures following muscle contractions in diabetic rat skeletal muscles: fiber-type specific effects
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DOI：
10.1152/ajpregu.00044.2015
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发表时间：
2015-07-15
影响因子：
2.8
通讯作者：
Kano, Yutaka
中科院分区：
文献类型：
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作者：
Eshima, Hiroaki;Poole, David C.;Kano, Yutaka
在1型糖尿病中，骨骼肌在肌肉收缩后静息细胞内钙离子浓度([Ca2+](I))的动态平衡受到破坏。目前还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条件。我们检验了以下假设：1)糖尿病大鼠慢抽动(I型)肌明显的静息[Ca~(2+)](I)升高会在快收缩(II型)肌中加剧；2)这些[Ca~(2+)](I)水平升高可能与微血管氧分压(PMV(O2))紊乱有关，而不是肌浆网功能障碍本身。成年雄性Wistar大鼠随机分为糖尿病(DIA)组和健康(CONT)组。4周后，持续电刺激(12 0 S，10 0 Hz)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。用Fura 2-AM在体内(即循环完整)进行钙离子成像。DIA增加了EDL的疲劳性(P<；0.05)，但不增加SOL。在恢复期，Sol[Ca~(2+)](I)要么在150 S内恢复到其静息基线(在600 S时为1.00+/-0.02)，要么在恢复期完全没有升高(DIA在600 S时为1.03+/-0.02，P&gT；0.05)。在恢复期，EDL cont[Ca~(2+)](I)也下降到与基础值(1.06+/-0.01，P>；0.05)无明显差异。与之形成鲜明对比的是，整个恢复期EDL DIA[Ca~(2+)](I)在整个恢复期都保持在较高水平(即，S 600时为1.23+/-0.03P<；0.05)。EDL DIA中[Ca~(2+)](I)不能恢复到基线水平与SR Ca~(2+)-ATPase(SERCA)1或SERCA2蛋白水平的降低无关(均升高30-40%，P<；0.05)。然而，在EDL中，PMV(O2)恢复动力学明显减慢，平均PMV(O2)显著降低(CONT 27.9+/-2.0vs DIA 18.4+/-2.0Torr，P<；0.05)，这一行为与升高的[Ca~(2+)](I)有关。相比之下，SOL(P+0.05)则不是这样，因为在DIA的恢复过程中，[Ca~(2+)](I)和PMV(O2)都没有出现紊乱。综上所述，糖尿病大鼠快抽动肌肉的[Ca~(2+)](I)动态平衡的恢复受到损害，但慢抽动肌肉的恢复并不伴随PMV(O2)压力的降低。
In Type 1 diabetes, skeletal muscle resting intracellular Ca2+ concentration ([Ca2+](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 [Ca2+](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 [Ca2+](i) levels would relate to derangement of microvascular partial pressure of oxygen (Pmv(O2)) 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). Ca2+ 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 [Ca2+](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 [Ca2+](i) also decreased to values not different from baseline (1.06 +/- 0.01, P > 0.05) at 600 s. In marked contrast, EDL DIA [Ca2+](i) remained elevated for the entire recovery period (i.e., 1.23 +/- 0.03 at 600 s, P < 0.05). The inability of [Ca2+](i) to return to baseline in EDL DIA was not associated with any reduction of SR Ca2+ -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 [Ca2+](i). In contrast, this was not the case for SOL (P+ 0.05) in that neither [Ca2+](i) nor Pmv(O2) were deranged in recovery with DIA. In conclusion, recovery of [Ca2+](i) homeostasis is impaired in diabetic rat fast-twitch but not slow-twitch muscle in concert with reduced Pmv(O2) pressures.