Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes
Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes
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DOI：
10.1126/science.1069982
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发表时间：
2002-03-01
期刊：
影响因子：
56.9
通讯作者：
Pozzan, T
中科院分区：
文献类型：
--
作者：
Zaccolo, M;Pozzan, T
第二信使环腺苷单磷酸（cAMP）是交感神经控制心脏收缩的最重要的调节剂。然而，在心肌细胞和许多其他细胞类型中，cAMP转导各种受体刺激后产生的信号并激活不同的细胞功能，这就提出了如何实现特异性的问题。在信号转导的一般领域，一种观点正在出现，即特异性是由信号事件的紧密定位保证的。在这里，我们发现在新生大鼠心肌细胞中，p -肾上腺素能刺激产生了多个微结构域，其cAMP浓度增加与横管/连接肌浆网膜区域相对应。受限制的cAMP池显示出大约1微米的作用范围，第二信使的自由扩散受到磷酸二酯酶活性的限制。此外，我们证明了这种cAMP梯度特异性地激活了锚定在T小管附近的蛋白激酶a分子子集。
The second messenger cyclic adenosine monophosphate (cAMP) is the most important modulator of sympathetic control over cardiac contractility. In cardiac myocytes and many other cell types, however, cAMP transduces the signal generated upon stimulation of various receptors and activates different cellular functions, raising the issue of how specificity can be achieved. In the general field of signal transduction, the view is emerging that specificity is guaranteed by tight localization of signaling events. Here, we show that in neonatal rat cardiac myocytes, P-adrenergic stimulation generates multiple microdomains with increased concentration of cAMP in correspondence with the region of the transverse tubule/junctional sarcoplasmic reticulum membrane. The restricted pools of cAMP show a range of action as small as approximately 1 micrometer, and free diffusion of the second messenger is limited by the activity of phosphodiesterases. Furthermore, we demonstrate that such gradients of cAMP specifically activate a subset of protein kinase A molecules anchored in proximity to the T tubule.