Effects of volatile anesthetics on store-operated Ca2+ influx in airway smooth muscle
Effects of volatile anesthetics on store-operated Ca2+ influx in airway smooth muscle
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DOI：
10.1097/00000542-200408000-00018
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发表时间：
2004-08-01
期刊：
影响因子：
8.8
通讯作者：
Sieck, GC
中科院分区：
文献类型：
--
作者：
Pabelick, CM;Ay, B;Sieck, GC
背景：在气道平滑肌（ASM）中，挥发性麻醉药通过增加Ca 2+“泄漏而消耗肌浆网（SR）的Ca 2+储存。因此，SR补充变得依赖于Ca 2+流入。SR Ca 2+库的耗尽通过特定的质膜通道（库操纵的Ca 2+通道（SOCC））触发Ca 2+内流。我们假设，麻醉剂抑制SOCC触发增加SR Ca 2+的“泄漏”，防止SR的补充和提高ASM relaxation.Methods：在猪ASM cells，SR Ca 2+消耗cyclopiazonic酸或咖啡因0细胞外Ca 2+，硝苯地平和KCl（防止Ca 2+内流通过L-型和SOCC通道）。细胞外Ca ~（2+）的快速引入选择性激活SOCC。SOCC激活后，补充SR，并在存在1或2种最小肺泡浓度氟烷、异氟烷或七氟烷的情况下重复该方案。在其他细胞中，SOCC的特点和乙酰胆碱（Ach）和挥发性anesthesiants.Results之间的相互作用：Cyclopiazonic酸产生缓慢的SR泄漏，而咖啡因的反应是短暂的ASM细胞。再引入细胞外Ca ~（2+）迅速增加[Ca ~（2+）]（i）。这种内流对硝苯地平、SKF-96365和KBR-7943不敏感，被Ni 2+和1，4，5-三磷酸肌醇诱导的SR Ca 2+释放的阻断所抑制，并被ACh增强。预先暴露于1或2个最小肺泡浓度氟烷完全抑制Ca 2+内流时，细胞外Ca 2+重新引入，而异氟烷和七氟烷产生较小的抑制。结论：挥发性麻醉药抑制了猪ASM细胞中Ni 2 +/La 3+敏感的钙池操作的Ca 2+内流机制，这可能有助于维持麻醉药诱导的支气管扩张。
Background: In airway smooth muscle (ASM), volatile anesthetics deplete sarcoplasmic reticulum (SR) Ca2+ stores by increasing Ca2+ "leak." Accordingly, SR replenishment becomes dependent on Ca2+ influx. Depletion of SR Ca2+ stores triggers Ca2+ influx via specific plasma membrane channels, store-operated Ca2+ channels (SOCC). We hypothesized that anesthetics inhibit SOCC triggered by increased SR Ca2+ "leak," preventing SR replenishment and enhancing ASM relaxation.Methods: In porcine ASM cells, SR Ca2+ was depleted by cyclopiazonic acid or caffeine in 0 extracellular Ca2+, nifedipine and KCl (preventing Ca2+ influx through L-type and SOCC channels). Extracellular Ca2+ was rapidly introduced to selectively activate SOCC. After SOCC activation, SR was replenished and the protocol repeated in the presence of 1 or 2 minimum alveolar concentration halothane, isoflurane, or sevoflurane. In other cells, characteristics of SOCC and interactions between acetylcholine (Ach) and volatile anesthetics were examined.Results: Cyclopiazonic acid produced slow SR leak, whereas the caffeine response was transient in ASM cells. Reintroduction of extracellular Ca2+ rapidly increased [Ca2+](i). This influx was insensitive to nifedipine, SKF-96365, and KBR-7943, inhibited by Ni2+ and blockade of inositol 1,4,5-triphosphate-induced SR Ca2+ release, and enhanced by ACh. Preexposure to 1 or 2 minimum alveolar concentration halothane completely inhibited Ca2+ influx when extracellular Ca2+ was reintroduced, whereas isoflurane and sevoflurane produced less inhibition. Only halothane and isoflurane inhibited ACh-induced augmentation of Ca2+ influx.Conclusion: Volatile anesthetics inhibit a Ni2+/La3+-sensitive store-operated Ca2+ influx mechanism in porcine ASM cells, which likely helps maintain anesthetic-induced bronchodilation.