Rüegg J C, Morano I
II. Physiologisches Institut, Universität Heidelberg, F.R.G.
J Cardiovasc Pharmacol. 1989;14 Suppl 3:S20-3. doi: 10.1097/00005344-198914003-00005.
Myocardial contractile force may be altered not only by changing intracellular free Ca2+ but also by increasing or decreasing the calcium responsiveness of the myofilaments. The latter effect may be due to interventions that decrease the calcium affinity of troponin C, such as intracellular acidosis or factors that act "downstream" of the calcium-troponin-C interaction in the process of muscle activation. These include inorganic phosphate, which accumulates under hypoxic conditions. Conversely, calcium responsiveness may be increased by drugs that probably increase the calcium affinity of troponin C, such as sulmazole, adibendan, pimobendan, and isomazole. These and related drugs also increase the force development of skinned trabeculae that are submaximally activated by Ca2+ stimulation in ATP salt solution. Thus, we confirmed earlier studies showing that adibendan increased submaximal Ca2+-activated force of pig-heart trabecula skinned by 0.5% lubrol-WX. Qualitatively similar results were obtained with pimobendan. However, calcium responsiveness may not only be modulated by factors influencing troponin, but also by modulation of crossbridge rate constants as well as by other factors that act downstream of troponin C. These include peptides derived from thin-filament proteins and subfragment S1 of myosin.
心肌收缩力不仅可通过改变细胞内游离钙离子浓度来改变，还可通过增加或降低肌丝对钙的反应性来改变。后一种效应可能是由于降低肌钙蛋白C对钙亲和力的干预措施，如细胞内酸中毒或在肌肉激活过程中作用于钙-肌钙蛋白-C相互作用“下游”的因素。这些因素包括在缺氧条件下积累的无机磷酸盐。相反，钙反应性可能会因可能增加肌钙蛋白C对钙亲和力的药物而增加，如舒马唑、阿迪苯旦、匹莫苯旦和异莫唑。这些药物及相关药物还可增加在ATP盐溶液中由钙离子刺激亚最大激活的去表皮小梁的力产生。因此，我们证实了早期的研究，即阿迪苯旦可增加用0.5%十二烷基肌氨酸钠去表皮的猪心小梁的亚最大钙离子激活力。匹莫苯旦也得到了定性相似的结果。然而，钙反应性不仅可能受影响肌钙蛋白的因素调节，还可能受横桥速率常数的调节以及肌钙蛋白C下游作用的其他因素调节。这些因素包括来自细肌丝蛋白的肽和肌球蛋白亚片段S1。
