Harrison Glenn J, van Wijhe Michiel H, de Groot Bas, Dijk Francina J, Gustafson Lori A, van Beek Johannes H G M
Heart Foundation Research Centre, Griffith University, Gold Coast, Queensland 9726, Australia.
Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H883-90. doi: 10.1152/ajpheart.00725.2002. Epub 2003 Apr 24.
Creatine kinase (CK) and glycolysis represent important energy-buffering processes in the cardiac myocyte. Although the role of compartmentalized CK in energy transfer has been investigated intensely, similar duties for intracellular glycolysis have not been demonstrated. By measuring the response time of mitochondrial oxygen consumption to dynamic workload jumps (tmito) in isolated rabbit hearts, we studied the effect of inhibiting energetic systems (CK and/or glycolysis) on transcytosolic signal transduction that couples cytosolic ATP hydrolysis to activation of oxidative phosphorylation. Tyrode-perfused hearts were exposed to 15 min of the following: 1) 0.4 mM iodoacetamide (IA; n = 6) to block CK (CK activity <3% vs. control), 2) 0.3 mM iodoacetic acid (IAA; n = 5) to inhibit glycolysis (GAPDH activity <3% vs. control), or 3) vehicle (control, n = 7) at 37 degrees C. Pretreatment tmito was similar across groups at 4.3 +/- 0.3 s (means +/- SE). No change in tmito was observed in control hearts; however, in IAA- and IA-treated hearts, tmito decreased by 15 +/- 3% and 40 +/- 5%, respectively (P < 0.05 vs. control), indicating quicker energy supply-demand signaling in the absence of ADP/ATP buffering by CK or glycolysis. The faster response times in IAA and IA groups were independent of the size of the workload jump, and the increase in myocardial oxygen consumption during workload steps was unaffected by CK or glycolysis blockade. Contractile function was compromised by IAA and IA treatment versus control, with contractile reserve (defined as increase in rate-pressure product during a standard heart rate jump) reduced to 80 +/- 8% and 80 +/- 10% of baseline, respectively (P < 0.05 vs. control), and significant elevations in end-diastolic pressure, suggesting raised ADP concentration. These results demonstrate that buffering of phosphate metabolites by glycolysis in the cytosol contributes appreciably to slower mitochondrial activation and may enhance contractile efficiency during increased cardiac workloads. Glycolysis may therefore play a role similar to CK in heart muscle.
肌酸激酶（CK）和糖酵解是心肌细胞中重要的能量缓冲过程。尽管已对分隔化的CK在能量转移中的作用进行了深入研究，但细胞内糖酵解的类似作用尚未得到证实。通过测量离体兔心脏中线粒体氧消耗对动态工作负荷跳跃（tmito）的响应时间，我们研究了抑制能量系统（CK和/或糖酵解）对跨胞质信号转导的影响，该信号转导将胞质ATP水解与氧化磷酸化的激活偶联起来。用Tyrode液灌注的心脏在37℃下暴露于以下情况15分钟：1）0.4 mM碘乙酰胺（IA；n = 6）以阻断CK（CK活性与对照相比<3%），2）0.3 mM碘乙酸（IAA；n = 5）以抑制糖酵解（甘油醛-3-磷酸脱氢酶活性与对照相比<3%），或3）溶剂（对照，n = 7）。各组预处理时的tmito相似，为4.3±0.3秒（平均值±标准误）。对照心脏中未观察到tmito的变化；然而，在IAA和IA处理的心脏中，tmito分别下降了15±3%和40±5%（与对照相比P<0.05），表明在缺乏CK或糖酵解对ADP/ATP的缓冲作用时，能量供需信号传递更快。IAA组和IA组更快的响应时间与工作负荷跳跃的大小无关，工作负荷增加期间心肌氧消耗的增加不受CK或糖酵解阻断的影响。与对照相比，IAA和IA处理损害了收缩功能，收缩储备（定义为标准心率跳跃期间速率-压力乘积的增加）分别降至基线的80±8%和80±10%（与对照相比P<0.05），舒张末期压力显著升高，提示ADP浓度升高。这些结果表明，胞质中糖酵解对磷酸代谢物的缓冲作用明显有助于减缓线粒体激活，并可能在心脏工作负荷增加期间提高收缩效率。因此，糖酵解在心肌中的作用可能与CK类似。
