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首页> 外文期刊>Cellular Signalling >AKAP150 participates in calcineurin/NFAT activation during the down-regulation of voltage-gated K+ currents in ventricular myocytes following myocardial infarction
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AKAP150 participates in calcineurin/NFAT activation during the down-regulation of voltage-gated K+ currents in ventricular myocytes following myocardial infarction

机译：在心肌梗死后，心室肌细胞中电压门控性K +电流下调期间，AKAP150参与钙调神经磷酸酶/ NFAT激活

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摘要

The Ca2+-responsive phosphatase calcineurin/protein phosphatase 2B dephosphorylates the transcription factor NFATc3. In the myocardium activation of NFATc3 down-regulates the expression of voltage-gated K+ (K-v) channels after myocardial infarction (MI). This prolongs action potential duration and increases the probability of arrhythmias. Although recent studies infer that calcineurin is activated by local and transient Ca2+ signals the molecular mechanism that underlies the process is unclear in ventricular myocytes. Here we test the hypothesis that sequestering of calcineurin to the sarcolemma of ventricular myocytes by the anchoring protein AKAP150 is required for acute activation of NFATc3 and the concomitant down-regulation of K-v channels following MI. Biochemical and cell based measurements resolve that approximately 0.2% of the total calcineurin activity in cardiomyocytes is associated with AKAP150. Electrophysiological analyses establish that formation of this AKAP150-calcineurin signaling dyad is essential for the activation of the phosphatase and the subsequent down-regulation of K-v channel currents following MI. Thus AKAP150-mediated targeting of calcineurin to sarcolemmal micro-domains in ventricular myocytes contributes to the local and acute gene remodeling events that lead to the down-regulation of K-v currents. (C) 2015 Elsevier Inc. All rights reserved.
机译：Ca2 +响应磷酸酶钙调磷酸酶/蛋白磷酸酶2B使转录因子NFATc3去磷酸化。在心肌中，NFATc3的激活下调心肌梗死（MI）后电压门控性K +（K-v）通道的表达。这延长了动作电位的持续时间并增加了心律不齐的可能性。尽管最近的研究表明钙调神经磷酸酶被局部和瞬时Ca2 +激活，但在心室肌细胞中尚不清楚该过程的分子机制。在这里，我们测试的假设是，锚定蛋白AKAP150将钙调神经磷酸螯合到心室肌细胞的肌膜是NFATc3的急性激活和MI后K-v通道随之下调所必需的。基于生化和细胞的测量结果证明，心肌细胞中约0.2％的钙调神经磷酸酶活性与AKAP150有关。电生理学分析表明，此AKAP150-钙调神经磷酸信号二联体的形成对于磷酸酶的激活以及MI后K-v通道电流的下调至关重要。因此，AKAP150介导的钙调神经磷酸酶靶向心室肌细胞中的肌膜微区有助于局部和急性基因重塑事件，从而导致K-v电流下调。 （C）2015 Elsevier Inc.保留所有权利。

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