Bers Donald M, Guo Tao
Department of Physiology, Loyola University Chicago, 2160 S. First Ave, Maywood, IL 60153, USA.
Ann N Y Acad Sci. 2005 Jun;1047:86-98. doi: 10.1196/annals.1341.008.
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.
钙（Ca）是多种细胞功能的多功能调节因子。在心肌中，钙是电激活、离子通道门控和兴奋-收缩（E-C）偶联的直接核心介质，所有这些过程都发生在毫秒时间尺度上。E-C偶联中的关键放大步骤受到非常局部的[Ca]的严格控制。钙还通过激酶和磷酸酶（如钙调蛋白依赖性蛋白激酶[CaMKII]和钙调神经磷酸酶）直接激活信号传导，这些过程发生在更长的时间尺度（几秒到几分钟）上，并且这些钙依赖性调节剂与其靶标以及钙的共定位在不同的信号通路中也至关重要。最后，钙依赖性信号传导还参与基因表达的长期（几分钟到几小时/天）改变（或兴奋-转录偶联）。这些途径与肥大和心力衰竭有关，并且它们可以改变一些参与E-C偶联的关键钙调节蛋白的表达以及它们受激酶和磷酸酶的调节。在这种核转录过程中可能再次涉及物理微环境，使得它们能够感知与E-C偶联中涉及的不同的离散钙信号。通过这种方式，细胞可以以多种方式利用钙信号传导，这些方式在空间和时间上以不同的方式发挥作用。
