Su Su-Wen, Xu Yan-Fang, Mei He-Shan, Qi Ya-Juan, Yin Jing-Xiang, Wang Chuan, Zhang Yong-Jian, Wang Yong-Li
Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
Yao Xue Xue Bao. 2008 Mar;43(3):259-66.
Effect of strophanthidin (Str) on intracellular calcium concentration ([Ca2+]i) was investigated on isolated ventricular myocytes of guinea pig. Single ventricular myocytes were obtained by enzymatic dissociation technique. Fluorescent signal of [Ca2+]i was detected with confocal microscopy after incubation of cardiomycytes in Tyrode' s solution with Fluo3-AM. The result showed that Str increased [Ca2+]i in a concentration-dependent manner. The ventricular myocytes began to round-up into a contracture state once the peak level of [Ca2+]i was achieved in the presence of Str (10 micromol L(- 1)), but remained no change in the presence of Str (1 and 100 nmol L(-1)). Tetrodotoxin (TTX), nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str (1 and 100 nmol L(-1)) , but had no obvious effects on the action of Str (10 micromol L(-1)). The elevation of [Ca2+]i caused by Str at all of the detected concentrations was partially antagonized by rynodine (10 micromol L(-1)) or the removal of Ca2+ from Tyrode's solution. In Na+, K+ -free Tyrode' s solution, the response of cardiomycytes in [Ca2+]i elevation to Str (10 micromol L(-1)) was attenuated, while remained no change to Str (1 and 100 nmol L(-1)). TTX, nisodipine, and high concentration of extracellular Ca2+ changed the response of cardiomycytes to Str at all of the detected concentrations in Na+, K+ -free Tyrode's solution. The study suggests that the elevation of [Ca2+]i by Str at the low (nomomolar) concentrations is partially mediated by the extracellular calcium influx through Ca2+ channel or a "slip mode conductance" of TTX sensitive Na+ channel. While the effect of Str at high (micromolar) concentrations was mainly due to the inhibition of Na+, K+ -ATPase. Directly triggering the release of intracellular Ca2+ from sarcoplasmic reticulum (SR) by Str may be also involved in the mechanism of [Ca2+]i elevation.
研究了毒毛花苷元（Str）对豚鼠离体心室肌细胞内钙浓度（[Ca2+]i）的影响。采用酶解技术分离单个心室肌细胞。将心肌细胞在含Fluo3-AM的台氏液中孵育后，用共聚焦显微镜检测[Ca2+]i的荧光信号。结果表明，Str以浓度依赖的方式增加[Ca2+]i。在Str（10 μmol/L）存在的情况下，一旦达到[Ca2+]i的峰值水平，心室肌细胞开始收缩成挛缩状态，但在Str（1和100 nmol/L）存在时保持不变。河豚毒素（TTX）、尼索地平及高浓度细胞外Ca2+改变了心肌细胞对Str（1和100 nmol/L）的反应，但对Str（10 μmol/L）的作用无明显影响。在所有检测浓度下，Str引起的[Ca2+]i升高均被雷诺丁（10 μmol/L）或从台氏液中去除Ca2+部分拮抗。在无Na+、K+的台氏液中，心肌细胞对Str（10 μmol/L）引起的[Ca2+]i升高反应减弱，而对Str（1和100 nmol/L）无变化。在无Na+、K+的台氏液中，TTX、尼索地平及高浓度细胞外Ca2+改变了心肌细胞对所有检测浓度Str的反应。该研究表明，低（纳摩尔）浓度的Str引起的[Ca2+]i升高部分是由细胞外钙通过Ca2+通道内流或TTX敏感Na+通道的“滑模电导”介导的。而高（微摩尔）浓度的Str的作用主要是由于抑制了Na+、K+-ATP酶。Str直接触发肌浆网（SR）释放细胞内Ca2+也可能参与了[Ca2+]i升高的机制。
