Hansford R G
Biochem J. 1987 Jan 1;241(1):145-51. doi: 10.1042/bj2410145.
The proportion of pyruvate dehydrogenase existing in the active form (PDHA) in suspensions of unstimulated cardiac myocytes oxidizing glucose is approx. 30%. Depolarization of the cells with concentrations of K+ above physiological values leads to an increase in the content of PDHA. Overloading of the cells with Na+ by treatment with veratridine and ouabain gives the same result. Each of these interventions is shown in experiments with Quin 2-loaded myocytes to lead to an increase in cytosolic free Ca2+ concentration ([Ca2+]c). Treatment of the cells with Ruthenium Red, an inhibitor of Ca2+ transport into mitochondria, largely prevents an increase in PDHA in response to addition of KCl or of veratridine plus ouabain. Ruthenium Red does not attenuate the increase in [Ca2+]c that occurs under these conditions. By contrast, treatment of the cells with ryanodine, an inhibitor of sarcoplasmic-reticulum Ca2+ transport and therefore of contraction, does not diminish the response of PDHA content to agents which raise [Ca2+]c; nor does loading of the cells with the Ca2+-chelating agent Quin 2, which also prevents contraction, at appropriate concentrations. It is concluded that an increase in [Ca2+]c causes an increase in PDHA content of cardiac myocytes independently of an increase in mechanical work. In the normal physiological situation the activation of dehydrogenases by Ca2+ is thought to help to maintain the balance of energy supply and demand during periods of increased work-load, which are associated with an increased myoplasmic [Ca2+]c.
在氧化葡萄糖的未受刺激心肌细胞悬液中，以活性形式存在的丙酮酸脱氢酶（PDHA）的比例约为30%。用高于生理值的K⁺浓度使细胞去极化会导致PDHA含量增加。用藜芦碱和哇巴因处理使细胞Na⁺过载也会得到相同结果。在使用负载喹啉2的心肌细胞进行的实验中，这些干预措施中的每一种都会导致胞质游离Ca²⁺浓度（[Ca²⁺]c）升高。用钌红（一种Ca²⁺转运到线粒体中的抑制剂）处理细胞，在很大程度上可防止因添加KCl或藜芦碱加哇巴因而导致的PDHA增加。钌红不会减弱在这些条件下发生的[Ca²⁺]c升高。相比之下，用ryanodine（一种肌浆网Ca²⁺转运抑制剂，因此也是收缩抑制剂）处理细胞，不会减少PDHA含量对升高[Ca²⁺]c的试剂的反应；在适当浓度下，用Ca²⁺螯合剂喹啉2负载细胞（这也会阻止收缩）也不会减少这种反应。可以得出结论，[Ca²⁺]c升高会导致心肌细胞PDHA含量增加，而与机械功增加无关。在正常生理情况下，Ca²⁺对脱氢酶的激活被认为有助于在与肌浆[Ca²⁺]c增加相关的工作负荷增加期间维持能量供需平衡。
