Effects of dantrolene sodium on intracellular Ca2+-handling in normal and Ca2+-overloaded cardiac muscle
Effects of dantrolene sodium on intracellular Ca2+-handling in normal and Ca2+-overloaded cardiac muscle
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DOI：
10.1016/s0014-2999(96)00678-4
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发表时间：
1996-12-05
影响因子：
5
通讯作者：
Morgan, JP
中科院分区：
文献类型：
--
作者：
Meissner, A;Szymanska, G;Morgan, JP
我们研究了丹曲林钠对正常和钙超载大鼠心肌细胞内钙稳态的影响。在加载有Ca 2+指示剂水母发光蛋白的等距收缩大鼠乳头肌中，丹曲林（50 μ M）产生轻度负性肌力作用（28 +/- 1.8至21 +/- 1.1 mN/mm（2）;平均值+/- S.E.; n = 6; P < 0.01），这被收缩期峰值[Ca 2 +]（i）的降低所抵消（0.81 +/- 0.04至0.67 +/- 0.04 μ M; P < 0.01）。在离体心肌肌浆网中，与对照制剂相比，丹曲林（50 μ M）使初始Ca 2+摄取率增加23%（pCa 6.2：46.9 +/- 1.6至61.1 +/-2.2 nmol/mg/min; n = 4; P < 0.001）。在异丙肾上腺素预处理（100 μ M）的制剂中，以1.0 Hz的刺激率（n = 12），[Ca 2 +]（0）= 5.0 mM，引起细胞内Ca 2+过载。舒张期Ca 2+振荡和后收缩分别增加平均舒张期[Ca 2 +]（i）（0.33 +/- 0.1至0.56 +/- 0.1 μ M）和张力（9.5 +/- 1.8至15.3 +/- 2.1 mN/mm（2））。加入丹曲林（50 μ M）可降低Ca 2+振荡和后收缩的幅度;平均舒张期[Ca 2 +]（i）降至0.44 +/- 0.1 μ M，舒张期张力降至13.5 +/- 2.2 mN/mm（2）。因此，我们得出结论，丹曲林钠通过心肌肌浆网改变Ca 2+处理，这种作用可能对[Ca 2 +]（i）稳态受损的心脏疾病有用。
We investigated the effects of dantrolene sodium on intracellular Ca2+ homeostasis in normal and Ca2+ overloaded rat cardiac muscle. In isometrically contracting rat papillary muscles loaded with the Ca2+ indicator aequorin, dantrolene (50 mu M) Produced a mild negative inotropic effect (28 +/- 1.8 to 21 +/- 1.1 mN/mm(2); mean +/- S.E.; n = 6; P < 0.01), which was paralleled by a decrease in peak systolic [Ca2+](i) (0.81 +/- 0.04 to 0.67 +/- 0.04 mu M; P < 0.01). In isolated cardiac sarcoplasmic reticulum, dantrolene (50 mu M) increased the initial Ca2+ uptake rate by 23% as compared to control preparations (at pCa 6.2: 46.9 +/- 1.6 to 61.1 +/- 2,2 nmol/mg per min; n = 4; P < 0.001). Intracellular Ca2+ overload was provoked in isoproterenol-pretreated (100 mu M) Preparations with [Ca2+](0) = 5.0 mM at a stimulation rate of 1.0 Hz (n = 12). Diastolic Ca2+ oscillations and aftercontractions increased mean diastolic [Ca2+](i) (0.33 +/- 0.1 to 0.56 +/- 0.1 mu M) and tension (9.5 +/- 1.8 to 15.3 +/- 2.1 mN/mm(2)), respectively. Addition of dantrolene (50 mu M) reduced the amplitude of Ca2+ oscillations and aftercontractions; mean diastolic [Ca2+](i) decreased to 0.44 +/- 0.1 mu M and diastolic tension to 13.5 +/- 2.2 mN/mm(2). We conclude, therefore, that dantrolene sodium modifies Ca2+ handling by the myocardial sarcoplasmic reticulum, an effect that might be useful in cardiac disorders with impaired [Ca2+](i) homeostasis.