Ca2+ oscillation frequency decoding in cardiac cell hypertrophy:: Role of calcineurin/NFAT as Ca2+ signal integrators
Ca2+ oscillation frequency decoding in cardiac cell hypertrophy:: Role of calcineurin/NFAT as Ca2+ signal integrators
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DOI：
10.1073/pnas.0712316105
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发表时间：
2008-02-26
影响因子：
11.1
通讯作者：
Pozzan, Tullio
中科院分区：
文献类型：
--
作者：
Colella, Matilde;Grisan, Francesca;Pozzan, Tullio
在体外培养的新生大鼠心肌细胞中研究了Ca 2+信号在触发肥大中的作用。我们发现，受体激动剂，如血管紧张素II，醛固酮，去甲肾上腺素和一个小的上升中KCl浓度，治疗缺乏对受体功能的直接影响引起的细胞大小和肌节重组的增加。所有这些处理增加了自发[Ca 2 +]瞬变的频率，引起转染的NFAT（GFP）的核转位，并增加了NFAT敏感的报告基因的表达。在这些条件下，在整个细胞或在核周区域的钙火花频率没有增加。钙调磷酸酶抑制剂环孢霉素A可抑制肥大和NFAT易位，但不能抑制[Ca 2 +]瞬变频率的增加。不同刺激引起的肥大对肌丝收缩的抑制不敏感。我们的结论是，钙调神经磷酸酶-NFAT可以作为收缩Ca 2+信号的积分器，并且它们可以解码频率的改变，即使是快速的Ca 2+振荡。
The role of Ca2+ signaling in triggering hypertrophy was investigated in neonatal rat cardiomyocytes in vitro. We show that an increase in cell size and sarcomere reorganization were elicited by receptor agonists such as Angiotensin II, aldosterone, and norepinephrine and by a small rise in medium KCI concentration, a treatment devoid of direct effects on receptor functions. All these treatments increased the frequency of spontaneous [Ca2+] transients, caused nuclear translocation of transfected NFAT(GFP), and increased the expression of a NFAT-sensitive reporter gene. There was no increase in Ca2+ spark frequency in the whole cell or in the perinuclear region under these conditions. Hypertrophy and NFAT translocation but not the increased frequency of [Ca2+] transients were inhibited by the calcineurin inhibitor cyclosporine A. Hypertrophy by the different stimuli was insensitive to inhibition of myofilament contraction. We concluded that calcineurin-NFAT can act as integrators of the contractile Ca2+ signal, and that they can decode alterations in the frequency even of rapid Ca2+ oscillations.