抑制SERCA活性减缓萎缩比目鱼肌间断强直收缩张力的下降(英文)

Inhibited SERCA Activity Retards Decline of Repeated Short Tetani Force in Atrophic Soleus

目的确定骨骼肌收缩的舒张时程可作为判断肌质网钙离子ATP酶(SERCA)活性的功能性指标,并探讨SERCA活性对后肢去负荷大鼠萎缩比目鱼肌间断强直收缩张力下降速率的调节作用。方法采用尾部悬吊大鼠模型,游离骨骼肌肌条进行灌流,观测收缩功能的改变。结果与对照组相比,去负荷4周萎缩比目鱼肌肌条在27℃灌流条件下,间断强直收缩的舒张时程(TR75)显著缩短,强直收缩张力快速下降。相反,采用SERCA活性抑制剂环匹阿尼酸(Cyclopiazonic Acid),可延长TR75时程,并恢复强直收缩张力下降速率至对照水平。较低灌流温度(22℃)降低对照大鼠比目鱼肌SERCA活性,同时减缓强直收缩张力的下降;较高温度(35℃)则产生相反的结果。低浓度咖啡因灌流不能改变萎缩比目鱼肌强直收缩下降速率;增加灌流液Ca2+浓度和钙离子载体A23187作用下,减慢强直收缩张力下降速率。结论缩短的TR75与萎缩比目鱼肌SERCA活性增加相关联,TR75可作为表征SERCA活性的功能性指标。适度抑制SERCA活性,可能通过提高肌纤维内Ca2+浓度,减缓强直收缩张力下降速率。

Objective To confirm that the relaxation duration can be used as a functional marker of sarcoplasmic reticulum Ca2＋-ATPase（SERCA） activity and to elucidate the role of SERCA activity on the rate of force decline during repeated short tetani in the atrophic soleus induced with electric-stimulated intermittent.Methods Tail-suspended rats were used to simulate weightlessness on the ground.The isolated muscle strips were perfused to measure the changes in contractile function.Results Four-week unloaded soleus showed a significant shortening in twitch and tetanic time-from-peak-force-to-75%-relaxation（TR75） and a faster decline of force in 27 ℃ perfusion condition compared with the control group.The shortened TR75 was related to a high SERCA activity in the unloaded soleus.On the contrary,cyclopiazonic acid,an inhibitor of SERCA,prolonged TR75 and reduced the rate of force decline to the control level in the unloaded soleus.Lower perfusion temperature（22 ℃） decreased SERCA activity and the rate of force decline,but higher temperature（35 ℃） did the opposing effects in the control soleus.The rate of force decline was not affected by low concentration of caffeine in the unloaded soleus.However,the elevated extracellular Ca2＋ concentration and A23187 reduced the rate of force decline in the unloaded soleus.Conclusion Reduced TR75 is related to high SERCA activity in atrophic soleus.TR75 may express the functional marker of SERCA activity.Slightly inhibited SERCA activity may maintain a higher Ca2＋ concentration of intracellular muscular fibers to reduce the rate of force decline in the titanic contraction.