The role of ATP produced by glycolysis in the maintenance of intramyocardial ion homeostasis

据报道，在心肌中，机械功的能量是由氧化磷酸化提供的，而维持离子稳态的能量是由糖酵解产生的。本研究探讨了糖酵解抑制对心肌细胞内钙稳态的影响。我们的结果表明，糖酵解ATP不是维持心肌钙稳态所必需的；糖酵解抑制所积累的磷酸糖可导致钙超载，但进一步的机制尚不清楚。同时对顿抑心肌的葡萄糖摄取进行了研究。短暂缺血后再灌流的心肌表现为无坏死的收缩功能障碍，称为“顿抑心肌”。据报道，顿抑心肌的糖酵解和糖生成增加，提示顿抑心肌对外源性葡萄糖的需求增加。这项研究还试图量化心肌葡萄糖摄取的增加，并阐明顿抑心肌葡萄糖摄取增加的途径。用其类似物2-脱氧葡萄糖替代葡萄糖后，用P-31核磁共振技术从大鼠心肌糖磷酸共振的时间历程定量葡萄糖摄取率。我们的结果表明，顿抑心肌的葡萄糖摄取增加与胰岛素刺激的心肌一样高，并且顿抑心肌的葡萄糖摄取增加是由葡萄糖转运蛋白维持的。临床应用F-18脱氧葡萄糖和正电子发射断层扫描证实急性心肌梗死患者再灌流心肌葡萄糖摄取增加。

It has been reported in myocardium that energy for mechanical work is provided by oxidative phosphorylation whereas that to maintain ion homeostasis is generated by glycolysis. In this study, the effects of glycolytic inhibition on intramyocardial calcium homeostasis was investigated. Our results indicate that glycolytic ATP is not necessary to maintain calcium homeostasis in myocardium ; the sugar phosphates accumulated by glycolytic inhibition induce the calcium overload, but the further mechanism was not clarified. The glucose uptake in stunned myocardium was also investigated. The myocardium reperfused after a brief period of ischemia shows contractile dysfunction without necrosis, and is called as "stunned myocardium." Glycolysis and glycogenesis have been reported to be augmented in stunned myocardium, suggesting that the demand for exogenous glucose is increased in stunned myocardium. This study also seeks to quantify the increase in myocardial glucose uptake and to clarify the pathway of augmented glucose uptake in stunned myocardium. Glucose uptake rate was quantified from the time course of sugar phosphate resonance in rat myocardium using P-31 nuclear magnetic resonanceafter substitution of glucose by its analogue, 2-deoxyglucose. Our results indicate that the glucose uptake in stunned myocardium is augmented as high as in the myocardium stimulated by insulin, and that the augmented glucose uptake in stunned myocardium is maintained by glucose transporter. The increase of glucose uptake in reperfused myocardium was also confirmed clinically in patients with acute myocardial infarction using F-18 fluorodeoxyglucose and positron emmission tomography.