Shimizu Juichiro, Yamashita Daisuke, Misawa Hiromi, Tohne Kiyoe, Matsuoka Satoshi, Kim Bongju, Takeuchi Ayako, Nakajima-Takenaka Chikako, Takaki Miyako
Department of Physiology II, Nara Medical University, Kashihara, 634-8521, Japan.
J Physiol Sci. 2009 Jan;59(1):63-74. doi: 10.1007/s12576-008-0006-6. Epub 2008 Dec 11.
The goal of our study was to evaluate the origin of the increased O(2) consumption in electrically stimulated left ventricular slices of isoproterenol-induced hypertrophied rat hearts with normal left ventricular pressure. O(2) consumption per minute (mVO(2)) of mechanically unloaded left ventricular slices was measured in the absence and presence of 1-Hz field stimulation. Basal metabolic mVO(2), i.e., mVO(2) without electrical stimulation, was significantly smaller, but mVO(2) for the total Ca(2+) handling in excitation-contraction coupling (E-C coupling mVO(2)), i.e., delta mVO(2) (=mVO(2) with stimulation - mVO(2) without stimulation), was significantly larger in the hypertrophied heart. Furthermore, the fraction of E-C coupling mVO(2) was markedly altered in the hypertrophied heart. Namely, mVO(2) consumed by sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) was depressed by 40%; mVO(2) consumed by the Na(+)/K(+)-ATPase (NKA)-Na(+)/Ca(2+) exchange (NCX) coupling was increased by 100%. The depressed mVO(2) consumption by SERCA2 was supported by lower protein expressions of phosphorylated-Ser(16) phospholamban and SERCA2. The increase in NKA-NCX coupling mVO(2) was supported by marked augmentation of NCX current. However, the increase in NCX current was not due to the increase in NCX1 protein expression, but was attributable to attenuation of the intrinsic inactivation mechanisms. The present results demonstrated that the altered origin of the increased E-C coupling mVO(2) in hypertrophy was derived from decreased SERCA2 activity (1ATP: 2Ca(2+)) and increased NCX activity coupled to NKA activity (1ATP: Ca(2+)). Taken together, we conclude that the energetically less efficient Ca(2+) extrusion pathway evenly contributes to Ca(2+) handling in E-C coupling in the present hypertrophy model.
我们研究的目的是评估在左心室压力正常的异丙肾上腺素诱导的肥大大鼠心脏的电刺激左心室切片中，氧气消耗增加的来源。在无1赫兹场刺激和有1赫兹场刺激的情况下，测量机械卸载的左心室切片每分钟的氧气消耗量（mVO₂）。基础代谢mVO₂，即无电刺激时的mVO₂，显著较小，但肥大心脏中兴奋-收缩偶联（E-C偶联）中总钙处理的mVO₂，即δmVO₂（=刺激时的mVO₂ - 无刺激时的mVO₂），显著较大。此外，肥大心脏中E-C偶联mVO₂的比例明显改变。具体而言，肌浆网钙ATP酶（SERCA2）消耗的mVO₂降低了40%；钠钾ATP酶（NKA）-钠钙交换（NCX）偶联消耗的mVO₂增加了100%。SERCA2消耗的mVO₂降低得到了磷酸化丝氨酸16受磷蛋白和SERCA2较低蛋白表达的支持。NKA-NCX偶联mVO₂的增加得到了NCX电流显著增强的支持。然而，NCX电流的增加不是由于NCX1蛋白表达的增加，而是由于内在失活机制的减弱。目前的结果表明，肥大中E-C偶联mVO₂增加的来源改变源于SERCA2活性降低（1ATP: 2Ca²⁺）和与NKA活性偶联的NCX活性增加（1ATP: Ca²⁺）。综上所述，我们得出结论，在本肥大模型中，能量效率较低的钙外排途径在E-C偶联的钙处理中起同等作用。
