Xestospongin C is a potent inhibitor of SERCA at a vertebrate synapse
Xestospongin C is a potent inhibitor of SERCA at a vertebrate synapse
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DOI：
10.1016/s0143-4160(02)00093-3
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发表时间：
2002-07-01
期刊：
影响因子：
4
通讯作者：
Robitaille, R
中科院分区：
文献类型：
--
作者：
Castonguay, A;Robitaille, R
用蛙神经肌肉接头研究了XeC对1，4，5-三磷酸肌醇（IP 3）受体的特异性作用。在突触周许旺细胞（PSC）中，该突触处的神经胶质细胞，Ca 2+储存依赖于IP 3激活。浴应用XeC（700 nM）引起短暂的钙升高，并阻断突触活性或各种激动剂（ATP，毒蕈碱，腺苷）引起的PSC中的Ca 2+反应，只有当Ca 2+商店先前已与局部应用激动剂的挑战。此外，XeC闭塞的影响毒胡萝卜素（tg; 2 μ M），阻断剂的Ca 2 + ATP酶泵的内部存储，未能引起Ca 2+瞬变后20分钟的暴露XeC。在神经末梢，其中的Ca 2+商店是ryanodine敏感的，XeC（700 nM）的应用程序延长了恢复期的Ca 2+瞬变诱发的单一动作电位，由于延长的Ca 2+清除在神经末梢。当在XeC（700 nM）之后应用于制剂时，没有观察到tg（2 μ M）对由神经刺激诱发的Ca 2+反应的影响。相反，XeC（700 nM）没有影响的形状和持续时间的Ca 2+进入神经末梢时，TG之前应用XeC。这些结果表明，XeC作为肌质/内质网Ca 2 + ATP酶（SERCA）泵的内部存储的抑制剂。(C)2002爱思唯尔科技有限公司。保留所有权利。
The specificity of action of Xestospongin C (XeC) towards the inositol 1,4,5-trisphosphate (IP3) receptor has been studied using the frog neuromuscular junction. In perisynaptic Schwann cells (PSCs), glial cells at this synapse, Ca2+ stores are dependent upon IP3 activation. Bath application of XeC (700 nM) caused a transient calcium elevation and blocked Ca2+ responses evoked in PSCs by synaptic activity or various agonists (ATP, muscarine, adenosine) only when Ca2+ stores had previously been challenged with local application of agonists. Moreover, XeC occluded the effects of thapsigargin (tg; 2 muM), a blocker of the Ca2+ ATPase pump of internal stores, which failed to evoke Ca2+ transients following 20 min of exposure to XeC. In nerve terminals, where the Ca2+ stores are ryanodine-sensitive, application of XeC (700 nM) prolonged the recovery phase of Ca2+ transients evoked by single action potentials, due to a prolonged Ca2+ clearance in the nerve terminal. No effects of tg (2 muM) were observed on Ca2+ response evoked by nerve stimulation when applied on the preparation after XeC (700 nM). Conversely, XeC (700 nM) had no effect on the shape and duration of Ca2+ entry in nerve terminals when tg was applied before XeC. These results indicate that XeC acts as an inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump of internal stores. (C) 2002 Elsevier Science Ltd. All rights reserved.