Tate C A, Hyek M F, Taffet G E
Department of Pharmacology, University of Houston, Texas.
Sports Med. 1991 Sep;12(3):208-17. doi: 10.2165/00007256-199112030-00005.
In its second messenger role in skeletal muscle, calcium coordinates the function of muscle (contractile activity) with its overall energetics, thereby controlling the provision of ATP in a time of need. Not only is ATP required for crossbridge turnover in the myofibrils, but it is also needed for the maintenance of ion pumps, nuclear activity, and so forth. When oxygen is limiting, the sustained contractions of both fast and slow muscle (after the immediate burst of activity) is primarily supported by glycogenolysis and the glycolytic pathway (anaerobic). Calcium is important to this process, and the compartmentation of the glycogen particle and some of the enzymes associated with the glycolytic pathway in the terminal cisternae of the sarcoplasmic reticulum ensures that the provision of glucose-6-phosphate to the glycolytic pathway for the generation of the needed ATP proceeds rapidly. The activation of phosphorylase and glycogenolysis by calcium-troponin-C is another example of the tight control of cellular energetics deemed possible by compartmentation within the cell. The regulation by calcium, therefore, is only dependent on the diffusion of calcium rather than diffusion of substrate. When oxygen is not limiting (i.e. when a new steady-state is reached), the aerobic metabolism of pyruvate and fatty acids may be regulated in part by calcium at least in slow skeletal muscle. Oxidative phosphorylation, where ADP is phosphorylated to ATP, is though to be controlled by the concentration of ADP in skeletal muscle. However, because of the obvious compartmentation of the mitochondria within the slow muscle fibre and the higher free calcium required for peak force development (5 mumol/L), the kinetics are theoretically favourable for the calcium cycle in slow muscle mitochondria to play an important role in the regulation of aerobic substrate oxidation, as it does in the heart. Although this hypothesis is attractive based on the available data, the direct demonstration of a major role for calcium as a regulator of substrate oxidation in slow muscle awaits experimentation.
在骨骼肌中作为第二信使时，钙将肌肉功能（收缩活动）与其整体能量代谢协调起来，从而在需要时控制ATP的供应。肌原纤维中的横桥周转不仅需要ATP，维持离子泵、核活性等也需要ATP。当氧气供应受限（即活动的即刻爆发之后），快肌和慢肌的持续收缩主要由糖原分解和糖酵解途径（无氧）来支持。钙对这一过程很重要，糖原颗粒以及肌浆网终池内一些与糖酵解途径相关的酶的区室化确保了向糖酵解途径提供葡萄糖-6-磷酸以生成所需ATP的过程能够迅速进行。钙-肌钙蛋白-C对磷酸化酶和糖原分解的激活是细胞内区室化实现对细胞能量代谢严格控制的另一个例子。因此，钙的调节仅依赖于钙的扩散而非底物的扩散。当氧气供应不受限（即达到新的稳态时），丙酮酸和脂肪酸的有氧代谢至少在慢骨骼肌中可能部分受钙的调节。氧化磷酸化过程中，ADP磷酸化为ATP，这一过程被认为受骨骼肌中ADP浓度的控制。然而，由于慢肌纤维中线粒体明显的区室化以及产生峰值力量所需的较高游离钙浓度（5微摩尔/升），从理论动力学角度来看，慢肌线粒体中的钙循环有利于在有氧底物氧化调节中发挥重要作用，就像在心脏中一样。尽管基于现有数据这一假设很有吸引力，但直接证明钙在慢肌中作为底物氧化调节因子的主要作用仍有待实验验证。
