Role of mitochondria in contraction and pacemaking in the mouse uterus
Role of mitochondria in contraction and pacemaking in the mouse uterus
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DOI：
10.1111/j.1476-5381.2010.00949.x
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发表时间：
2010-11-01
影响因子：
7.3
通讯作者：
van Helden, D. F.
中科院分区：
文献类型：
--
作者：
Gravina, F. S.;Parkington, H. C.;van Helden, D. F.
背景和目的人们对子宫自发收缩和起搏知之甚少。本研究探讨了线粒体Ca ~（2+）库在子宫活动中的作用。实验方法我们研究了线粒体和肌质内质网（SER）抑制剂对子宫收缩、膜电位（Vm）和胞浆Ca ~（2+）浓度的影响[Ca 2 +]（c）在小鼠子宫纵向平滑肌中的作用。关键词线粒体药物鱼藤酮，羰基氰-3-氯苯腙（CCCP），7-氯-5-（2-氯苯基）-1，5-二氢-4，1-苯并硫氮杂卓-2（3 H）-酮（CGP 37157）和山奈酚降低收缩力。ATP合成酶抑制剂寡霉素无明显影响。并与SER抑制剂环匹阿尼酸（CPA）、2-氨基乙氧基苯硼酸酯（2-APB）和咖啡因进行了比较。除CPA和寡霉素外，所有药物均降低收缩力。CPA和CCCP短暂增加收缩频率，恢复到对照水平，而鱼藤酮，CGP 37157，山奈酚和2-APB降低频率和咖啡因没有显着影响。应用程序的线粒体代理商时，CPA功能抑制商店没有改变收缩频率，但山奈酚除外，力下降。CCCP分别引起动情期和动情间期组织去极化和维持[Ca ~（2+）]（c）增加或去极化/短暂超极化和[Ca ~（2+）]（c）短暂增加。鱼藤酮引起超极化并维持[Ca 2 +]的增加（c）。CGP 37157和山奈酚引起超极化，但[Ca 2 +]没有可测量的变化（c）。一系列的K+通道阻滞剂的应用表明，在CCCP和CGP 37157诱导action.CONCLUSIONS和IMPLICATIONSMitochondria的作用钙激活的K+（K-Ca）通道的作用对子宫收缩有调节作用，与线粒体的抑制减少收缩幅度和起搏频率的变化Vm，[Ca 2 +]（c）和/或Ca 2+内流。
BACKGROUND AND PURPOSEUterine spontaneous contraction and pacemaking are poorly understood. This study investigates the role of the mitochondrial Ca2+ store in uterine activity.EXPERIMENTAL APPROACHWe investigated the effects of mitochondrial and sarco-endoplasmic reticulum (SER) inhibitors on contraction, membrane potential (Vm) and cytosolic Ca2+ concentration ([Ca2+](c)) in longitudinal smooth muscle of the mouse uterus.KEY RESULTSThe mitochondrial agents rotenone, carbonylcyanide-3-chlorophenylhydrazone (CCCP), 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157) and kaempferol decreased the force of contractions. The ATP synthase inhibitor oligomycin had no significant effect. The effects of these agents were compared with those of SER inhibitors cyclopiazonic acid (CPA), 2-amino ethoxyphenylborate (2-APB) and caffeine. All agents, except CPA and oligomycin, decreased contractile force. CPA and CCCP transiently increased contraction frequency, which returned to control levels, whereas rotenone, CGP37157, kaempferol and 2-APB decreased frequency and caffeine had no significant effect. Application of the mitochondrial agents when CPA functionally inhibited stores did not change contraction frequency but, with the exception of kaempferol, decreased force. CCCP caused depolarization and maintained increase in [Ca2+](c) or depolarization/transient hyperpolarization and transient increase in [Ca2+](c) for oestrus and di-oestrus tissues respectively. Rotenone caused hyperpolarization and maintained increase in [Ca2+](c). CGP37157 and kaempferol caused hyperpolarization but no measurable change in [Ca2+](c). Application of a range of K+ channel blockers indicated a role of Ca2+-activated K+ (K-Ca) channels in the CCCP- and CGP37157-induced actions.CONCLUSIONS AND IMPLICATIONSMitochondria have a modulatory role on uterine contractions, with mitochondrial inhibition reducing contraction amplitude and pacemaker frequency by changes in Vm, [Ca2+](c) and/or Ca2+ influx.