Calcium signaling in cardiac ventricular myocytes
Calcium signaling in cardiac ventricular myocytes
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DOI：
10.1196/annals.1341.008
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Guo, T
中科院分区：
文献类型：
--
作者：
Bers, DM;Guo, T
钙（Ca）是多种细胞功能的多功能调节剂。在心肌中，Ca是电激活、离子通道门控和兴奋-收缩（E-C）偶联的直接中枢介质，所有这些都在毫秒时间尺度上发生。在E-C耦合中的关键放大步骤是在非常局部的[Ca]的严格控制下。Ca还通过激酶和磷酸酶（例如，Ca-钙调蛋白依赖性蛋白激酶[CaMKII]和钙调神经磷酸酶），在较长的时间尺度（秒至分钟）内发生，这些Ca依赖性调节剂与其靶点和Ca的共定位在不同的信号传导途径中也是至关重要的。最后，钙依赖性信号也参与基因表达（或兴奋-转录偶联）的长期（数分钟至数小时/天）改变。这些途径参与肥大和心力衰竭，并且它们可以改变参与E-C偶联的一些关键Ca调节蛋白的表达及其通过激酶和磷酸酶的调节。在这种核转录中可能再次涉及物理微环境，使得它们感测与E-C偶联中所涉及的不同的离散Ca信号。以这种方式，细胞可以以多种方式使用Ca信号传导，这些方式以空间和时间上不同的方式起作用。
Calcium (Ca) is a multifunctional regulator of diverse cellular functions. In cardiac muscle Ca is a direct central mediator of electrical activation, ion channel gating, and excitation-contraction (E-C) coupling that all occur on the millisecond time scale. The key amplification step in E-C coupling is under tight control of very local [Ca]. Ca also directly activates signaling via kinases and phosphatases (e.g., Ca-calmodulin-dependent protein kinase [CaMKII] and calcineurin) that occur over a longer time scale (seconds to minutes), and the co-localization of these Ca-dependent modulators to their targets and to Ca is also critical in distinct signaling pathways. Finally, Ca-dependent signaling is also involved in long-term (minutes to hours/days) alterations in gene expression (or excitation-transcription coupling). These pathways are involved in hypertrophy and heart failure, and they can alter the expression of some of the key Ca regulatory proteins involved in E-C coupling and their regulation by kinases and phosphatases. There may again be physical microenvironments involved in this nuclear transcription, such that they sense a discrete Ca signal that is distinct from that involved in E-C coupling. In this way cells can use Ca signaling in multiple ways that function in spatially and temporally distinct manners.