Calcium-calmodulin dependent protein kinase II (CaMKII): a main signal responsible for early reperfusion arrhythmias.
Calcium-calmodulin dependent protein kinase II (CaMKII): a main signal responsible for early reperfusion arrhythmias.
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钙 - 钙调蛋白依赖性蛋白激酶II（CAMKII）：负责早期再灌注心律不齐的主要信号。
DOI：
10.1016/j.yjmcc.2011.08.010
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发表时间：
2011-12
影响因子：
5
通讯作者：
Mattiazzi A
中科院分区：
文献类型：
--
作者：
Said M;Becerra R;Valverde CA;Kaetzel MA;Dedman JR;Mundiña-Weilenmann C;Wehrens XH;Vittone L;Mattiazzi A
为了探索CaMK II依赖性磷酸化事件是否介导再灌注心律失常，Langendorff灌注心脏进行全脑缺血/再灌注。记录心外膜单相或跨膜动作电位和收缩力。在大鼠心脏中，再灌注显著增加了相对于缺血前值的过早搏动（PB）的数量。这种代谢模式与肌浆网（SR）Ca 2+释放通道（RyR 2）上Ser 2814和受磷蛋白（PLN）上Thr 17的CaMK II依赖性磷酸化显著增加相关。这些现象可以通过CaMKII抑制剂KN-93来预防。在SR膜靶向抑制CaMK II的转基因小鼠（SR-AIP）中，PB从31 ± 6次/3 min显著降低至5 ± 1次/3 min，早期后除极（埃兹）几乎完全消失。在RyR 2上的CaMKII磷酸化位点（RyR 2-S2814 A）基因突变的小鼠中，PB减少51.0 ± 14.7%。与此相反，在两个PLN磷酸化位点消融的转基因小鼠（PLN-DM）中，再灌注后PB的数量没有变化。在SR-AIP小鼠中的实验（其中CaMKII抑制剂肽锚定在SR膜中，但也抑制CaMKII对L型Ca 2+通道的调节）表明SR蛋白和/或L型Ca 2+通道的CaMKII依赖性磷酸化在再灌注心律失常中的关键作用。RyR 2-S2814 A中的实验进一步表明，高达60%的与CaMK II相关的PB依赖于RyR 2 Ser 2814位点的磷酸化，并且可以归因于延迟后去极化（DAD）。此外，PLN-Thr 17和L型Ca 2+通道的磷酸化可能通过增加SR Ca 2+含量和Ca 2+内流而参与再灌注诱导的PBs。
To explore whether CaMKII-dependent phosphorylation events mediate reperfusion arrhythmias, Langendorff perfused hearts were submitted to global ischemia/reperfusion. Epicardial monophasic or transmembrane action potentials and contractility were recorded. In rat hearts, reperfusion significantly increased the number of premature beats (PBs) relative to pre-ischemic values. This arrhythmic pattern was associated with a significant increase in CaMKII-dependent phosphorylation of Ser2814 on Ca2+-release channels (RyR2) and Thr17 on phospholamban (PLN) at the sarcoplasmic reticulum (SR). These phenomena could be prevented by the CaMKII-inhibitor KN-93. In transgenic mice with targeted inhibition of CaMKII at the SR membranes (SR-AIP), PBs were significantly decreased from 31 ± 6 to 5 ± 1 beats/3 min with a virtually complete disappearance of early-afterdepolarizations (EADs). In mice with genetic mutation of the CaMKII phosphorylation site on RyR2 (RyR2-S2814A), PBs decreased by 51.0 ± 14.7 %. In contrast, the number of PBs upon reperfusion did not change in transgenic mice with ablation of both PLN phosphorylation sites (PLN-DM). The experiments in SR-AIP mice, in which the CaMKII inhibitor peptide is anchored in the SR membrane but also inhibits CaMKII regulation of L-type Ca2+ channels, indicated a critical role of CaMKII-dependent phosphorylation of SR proteins and/or L-type Ca2+ channels in reperfusion arrhythmias. The experiments in RyR2-S2814A further indicate that up to 60% of PBs related to CaMKII are dependent on the phosphorylation of RyR2 Ser2814 site and could be ascribed to delayed-afterdepolarizations (DADs). Moreover, phosphorylation of PLN-Thr17 and L-type Ca2+ channels might contribute to reperfusion-induced PBs, by increasing SR Ca2+ content and Ca2+ influx.
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影响因子：
37.8
作者：
POGWIZD, SM;CORR, PB
通讯作者：
CORR, PB
影响因子：
10.8
作者：
Mundiña-Weilenmann, C;Ferrero, P;Mattiazzi, A
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Mattiazzi, A
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2.8
作者：
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64.5
作者：
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影响因子：
4.8
作者：
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