Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle

Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle
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DOI:
10.1152/ajpgi.00415.2007
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发表时间:
2008-02-01
影响因子:
4.5
通讯作者:
Mawe, Gary M.
Mawe, Gary M.
中科院分区:
医学2区
文献类型:
--
作者:
Balemba, Onesmo B.;Bartoo, Aaron C.;Mawe, Gary M.

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线粒体Ca 2+处理与Cajal平滑肌和间质细胞的自发节律活动有关。在这项研究中,我们评估了线粒体抑制剂对胆囊平滑肌(GBSM)自发动作电位(AP),Ca 2+闪光和Ca 2+波的影响。破坏线粒体膜电位与羰基氰化物3-氯苯腙,羰基氰化物4-(三氟甲氧基)苯腙,鱼藤酮,和抗霉素A显着减少或消除AP,Ca 2+闪光,和Ca 2+波GBSM。寡霉素阻断ATP的产生不改变AP或Ca 2+闪光,但显着降低Ca 2+波频率。分别用Ru 360和CGP-37157抑制线粒体Ca 2+摄取和Ca 2+释放,降低GBSM中Ca 2+闪光和Ca 2+波的频率。与寡霉素相似,环孢菌素A不改变AP和Ca ~(2+)闪光频率,但显著降低Ca ~(2+)波活性。这些数据表明,线粒体Ca 2+处理是必要的自发电活动的产生,因此可能在胆囊张力和运动性中发挥重要作用。
Mitochondrial Ca2+ handling has been implicated in spontaneous rhythmic activity in smooth muscle and interstitial cells of Cajal. In this investigation we evaluated the effect of mitochondrial inhibitors on spontaneous action potentials (APs), Ca2+ flashes, and Ca2+ waves in gallbladder smooth muscle ( GBSM). Disruption of the mitochondrial membrane potential with carbonyl cyanide 3-chlorophenylhydrazone, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone, rotenone, and antimycin A significantly reduced or eliminated APs, Ca2+ flashes, and Ca2+ waves in GBSM. Blockade of ATP production with oligomycin did not alter APs or Ca2+ flashes but significantly reduced Ca2+ wave frequency. Inhibition of mitochondrial Ca2+ uptake and Ca2+ release with Ru360 and CGP-37157, respectively, reduced the frequency of Ca2+ flashes and Ca2+ waves in GBSM. Similar to oligomycin, cyclosporin A did not alter AP and Ca2+ flash frequency but significantly reduced Ca2+ wave activity. These data suggest that mitochondrial Ca2+ handling is necessary for the generation of spontaneous electrical activity and may therefore play an important role in gallbladder tone and motility.