山莨菪碱抑制成年大鼠离体心室肌细胞钙瞬变和收缩及其机制

Inhibition effects and mechanisms of anisodamine on calcium transient and contractile function in isolated adult rat ventricular myocytes

目的:观察山莨菪碱对大鼠离体心室肌细胞钙瞬变和收缩功能的影响并探讨其机制。方法:采用单细胞动缘探测系统和双激发荧光光电倍增系统观察山莨菪碱对大鼠离体心室肌细胞钙瞬变和收缩功能的影响,应用信号转导通路中相关受体的激动剂或拮抗剂探讨其作用机制。结果:山莨菪碱1×10-9、1×10-7、1×10-5mol·L-1可直接抑制心室肌细胞钙瞬变和收缩功能;卡巴胆碱可以消除山莨菪碱的作用,而IP3受体阻断剂肝素(1×10-6mol·L-1)和细胞膜电压依赖型钙离子通道阻滞剂维拉帕米(1×10-6mol·L-1)可以减弱山莨菪碱的作用。结论:山莨菪碱抑制心室肌细胞钙瞬变和收缩功能可能与其阻断M受体、抑制细胞内钙库钙离子释放和经过电压依赖型钙离子通道的钙离子内流有关。

AIM: To study the effects and mechanisms of anisodamine on calcium transient and contractile function in isolated adult rat ventricular myocytes. METHODS: Single cell edge motion detection system and dual-excitation fluorescence photomultiplier system were used for measuring the intracellular calcium transient properties and contractile function. ΔFR, TTP, T_ 50D, PS, TPS, TR_ 90 and ±d_L/d_t were recorded by the ionoptix system. Antagonist of IP_3 receptor, VDCC and muscarinic receptors were used for study the mechanism of anisodamine. RESULTS: Anisodamine (1×10 -9,1×10 -7,1×10 -5 mol·L -1) directly inhibited intracellular calcium transient and contractile function. Carbachol (1×10 -6 mol·L -1) abolished the effect of anisodamine. Heparin (1×10 -6 mol·L -1) and verapamil (1×10 -6 mol·L -1) decreased the effect of anisodamine. CONCLUSION: The effect of anisodamine on intracellular calcium transient and contractile function may be related to inhibition of calcium releasing from intracellular calcium pool and VDCC.