Rüegg J C
Circulation. 1986 Mar;73(3 Pt 2):III78-84.
In cardiac muscle the relationship between contraction and the intracellular free calcium concentration is not unique but may vary over a wide range, as when influenced by new positive inotropic drugs. Modulation of the sensitivity of myofilaments to calcium may be studied in chemically skinned fibers devoid of a functional sarcoplasmic reticulum and in which the ionic composition of the interfilament space can be controlled and influenced at will. At low levels of activation with Ca++ (1 microM), the new nonglycosidic, nonadrenergic cardiotonic drugs sulmazole (AR-L 115 BS) and pimobendane (UD-CG 115 BS) increase calcium-induced contraction of skinned mammalian cardiac fibers by 30% to 50% in concentrations at which they exert a positive inotropic effect in vivo. The effect on skinned fibers is due to an increase in the sensitivity of the myofilaments to calcium and, at least in the case of sulmazole, may be attributed to an increase in calcium affinity of troponin. Calcium-induced contraction of skinned fibers from vertebrate smooth muscle that lacks troponin is not activated by sulmazole and pimobendane. Thus the positive inotropic action of these new cardiotonic drugs might be accounted for in part by their calcium-sensitizing action of myofilaments, although other mechanisms that increase intracellular free calcium may be involved as well.
在心肌中，收缩与细胞内游离钙浓度之间的关系并非单一，而是可能在很宽的范围内变化，如新的正性肌力药物影响时。肌丝对钙的敏感性调节可在去除功能性肌浆网的化学去表皮纤维中进行研究，在这种纤维中，肌丝间空间的离子组成可随意控制和影响。在低水平Ca++（1微摩尔）激活时，新型非糖苷、非肾上腺素能强心药物舒马唑（AR-L 115 BS）和匹莫苯丹（UD-CG 115 BS）在体内发挥正性肌力作用的浓度下，可使去表皮哺乳动物心脏纤维的钙诱导收缩增加30%至50%。对去表皮纤维的作用是由于肌丝对钙的敏感性增加，至少就舒马唑而言，可能归因于肌钙蛋白对钙的亲和力增加。舒马唑和匹莫苯丹不会激活缺乏肌钙蛋白的脊椎动物平滑肌去表皮纤维的钙诱导收缩。因此，这些新型强心药物的正性肌力作用可能部分归因于它们对肌丝的钙敏化作用，尽管也可能涉及其他增加细胞内游离钙的机制。
