Sevoflurane protects ventricular myocytes from Ca2+paradox-mediated Ca2+overload by blocking the activation of transient receptor potential canonical channels
Sevoflurane protects ventricular myocytes from Ca2+paradox-mediated Ca2+overload by blocking the activation of transient receptor potential canonical channels
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七氟烷通过阻断瞬时受体电位经典通道的激活，保护心室肌细胞免受 Ca2 悖论介导的 Ca2 超载
DOI：
10.1097/aln.0b013e31822b7901
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发表时间：
2011
期刊：
影响因子：
8.8
通讯作者：
Nosaka S
中科院分区：
文献类型：
--
作者：
Kojima A;Kitagawa H;Omatsu-Kanbe M,Matsuura H;Nosaka S
背景：挥发性麻醉药通过减弱细胞内钙超载而产生心脏保护作用。Ca 2悖论是研究Ca 2超负荷介导的心肌损伤机制的重要模型，最近发现Ca 2内流通过瞬时受体电位经典通道介导。本研究探讨了七氟醚对Ca 2反常现象的细胞机制的影响。方法：在Fluo-3或Mag-Fluo-4负载的小鼠心室肌细胞中，使用共聚焦激光扫描显微镜，在无和有七氟醚的情况下，在Ca 2耗竭15 min后，在Ca 2再充盈时检查Ca 2反常现象。Ca 2悖论引起约65%的肌细胞后，Ca 2再充盈，确定了突然升高的胞浆Ca 2伴随着过度挛缩。在Ca 2补充之前和期间（Post）或在Ca 2耗尽和补充期间（Postlong）给予七氟烷3 min可显著抑制Ca 2反常，Postlong比Post应用更有益。在Ca 2耗尽期间，肌浆网Ca 2水平逐渐降低，肌浆网Ca 2水平降低的肌细胞中很容易诱发Ca 2悖论。七氟烷的后给药（但非后给药）通过阻断Ryanodine受体的Ca 2泄漏来防止肌浆网Ca 2水平降低。全细胞膜片钳记录显示，七氟烷迅速阻断thapsiglavin诱导的瞬时受体电位典型电流。结论：七氟烷通过阻断瞬时受体电位典型通道和防止肌浆网Ca 2水平降低（与瞬时受体电位典型通道的激活较少相关），保护心室肌细胞免受Ca 2反常介导的Ca 2超负荷。
Background: Volatile anesthetics produce cardioprotective action by attenuating cellular Ca2 overload. The Ca2 paradox is an important model for studying the mechanisms associated with Ca2 overload-mediated myocardial injury, and was recently found to be mediated by Ca2 entry through the transient receptor potential canonical channels upon Ca2 repletion. This study investigated the effect of sevoflurane on cellular mechanisms underlying the Ca2 paradox.Methods: The Ca2 paradox was examined in fluo-3 or mag-fluo-4-loaded mouse ventricular myocytes using confocal laser scanning microscope, upon Ca2 repletion after 15 min of Ca2 depletion in the absence and presence of sevoflurane.Results: The Ca2 paradox was evoked in approximately 65% of myocytes upon Ca2 repletion, as determined by an abrupt elevation of cytosolic Ca2 accompanied by hypercontracture. The Ca2 paradox was significantly suppressed by sevoflurane administered for 3 min before and during Ca2 repletion (Post) or during Ca2 depletion and repletion (Postlong), and Postlong was more beneficial than Post application. The sarcoplasmic reticulum Ca2 levels gradually decreased during Ca2 depletion, and the Ca2 paradox was readily evoked in myocytes with reduced sarcoplasmic reticulum Ca2 levels. Postlong but not Post application of sevoflurane prevented decrease in sarcoplasmic reticulum Ca2 levels by blocking Ca2 leak through ryanodine receptors. Whole cell patch-clamp recordings revealed that sevoflurane rapidly blocked thapsigargin-induced transient receptor potential canonical currents. Conclusions: Sevoflurane protects ventricular myocytes from Ca2 paradox-mediated Ca2 overload by blocking transient receptor potential canonical channels and by preventing the decrease in sarcoplasmic reticulum Ca2 levels, which is associated with less activation of transient receptor potential canonical channels.