An acute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle
An acute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle
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DOI：
10.1113/jphysiol.2004.079939
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发表时间：
2005-06-01
影响因子：
5.5
通讯作者：
Gibala, MJ
中科院分区：
文献类型：
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作者：
Dawson, KD;Baker, DJ;Gibala, MJ
我们测试了一个假设，即在收缩过程中肌肉TCA循环中间产物的急性减少会损害有氧能量的传递。将雄性Wistar大鼠麻醉，分离一条腿的腓肠肌-跖肌-比目鱼肌（GPS）复合体，并用含有盐水（Con）或环丝氨酸（Cyclo; 0.05 mg g（-1），丙氨酸氨基转移酶（AAT）抑制剂）的红细胞培养基灌注。灌注1小时后，将GPS肌肉快速冷冻（Con-Rest，n = 11; Cyclo-Rest，n = 9）或刺激收缩10分钟（1 Hz，0.3 ms，2 V），血流固定在30 ml min（-1）（100 g）（-1），然后快速冷冻（Con-Stim，n = 10; Cyclo-Stim，n = 10）。在两个Cyclo-treated组中，最大AAT活性降低> 80%（P < 0.001）（静息：0.61 +/- 0.02;刺激：0.63 +/- 0.01 mmol（kg湿重）（-1）min（-1）;平均值+/- S.E.M.）与对照组相比（静息：3.56 +/- 0.16;刺激：3.92 +/- 0.29）。Cyclo-Rest与Con-Rest相比，5次测量TCAI（Sigma TCAI）的总和降低了23%，但无差异（P = 0.08）。然而，收缩10分钟后，Cyclo-Stim组的Sigma TCAI比Con-Stim组低25%（P = 0.006）（1.88 +/- 0.15 vs 2.48 +/- 0.11 mmol（kg干重）（-1））。尽管Cyclo治疗后TCAI急剧下降，但与对照组相比，非氧化能量供应标志物（磷酸肌酸、ATP和乳酸盐）的收缩诱导变化和刺激10分钟后张力下降相似。这些数据不支持TCAI的总肌肉浓度与收缩期间线粒体呼吸速率存在因果关系的假设。
We tested the hypothesis that an acute decrease in muscle TCA cycle intermediates during contraction would compromise aerobic energy delivery. Male Wistar rats were anaesthetized and the gastrocnemius-plantaris-soleus (GPS) muscle complex from one leg was isolated and perfused with a red cell medium containing either saline (Con) or cycloserine (Cyclo; 0.05 mg g(-1)), an inhibitor of alanine aminotransferase (AAT). After 1 h of perfusion, the GPS muscle was either snap frozen (Con-Rest, n = 11; Cyclo-Rest, n = 9) or stimulated to contract for 10 min (1 Hz, 0.3 ms, 2 V) with blood flow fixed at 30 ml min(-1) (100 g)(-1) and then snap frozen (Con-Stim, n = 10; Cyclo-Stim, n = 10). Maximal AAT activity was > 80% lower (P < 0.001) in both Cyclo-treated groups (Rest: 0.61 +/- 0.02; Stim: 0.63 +/- 0.01 mmol (kg wet wt)(-1) min(-1); mean +/- S.E.M.) compared to Con (Rest: 3.56 +/- 0.16; Stim: 3.92 +/- 0.29). The sum of five measured TCAI (Sigma TCAI) was reduced by 23% in Cyclo-Rest versus Con-Rest but this was not different (P = 0.08). However, after 10 min of contraction, the Sigma TCAI was 25% lower (P = 0.006) in Cyclo-Stim compared to Con-Stim (1.88 +/- 0.15 versus 2.48 +/- 0.11 mmol (kg dry wt)(-1)). Despite the acute decrease in TCAI after Cyclo treatment, the contraction-induced changes in markers of non-oxidative energy provision (phosphocreatine, ATP and lactate) and the decline in tension after 10 min of stimulation were similar compared to Con. These data do not support the hypothesis that the total muscle concentration of TCAI is causally linked to the rate of mitochondrial respiration during contraction.