Calcium and IP3 dynamics in cardiac myocytes: experimental and computational perspectives and approaches.
Calcium and IP3 dynamics in cardiac myocytes: experimental and computational perspectives and approaches.
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DOI：
10.3389/fphar.2014.00035
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发表时间：
2014
影响因子：
5.6
通讯作者：
Michailova AP
中科院分区：
文献类型：
--
作者：
Hohendanner F;McCulloch AD;Blatter LA;Michailova AP
钙离子在兴奋-收缩偶联（ECC）中起着至关重要的作用，但它也是一个关键的第二信使，在称为兴奋-转录偶联（ETC）的过程中激活Ca 2+依赖性转录因子。在过去的十年中积累的证据表明，肌醇1，4，5-三磷酸受体（IP 3R）介导的Ca 2+释放在细胞质和核Ca 2+信号的调节中起着关键作用。IP 3通过刺激与磷脂酶C（PLC）偶联的质膜受体产生，从而从磷脂酰肌醇4，5-二磷酸（PIP 2）释放IP 3。IP 3信号传导的一个有趣的方面是整个PIP 2-PLC-IP 3信号传导级联的存在以及在核被膜（NE）的内膜和外膜处IP 3R的存在，所述核被膜（NE）用作Ca 2+储存。细胞核被其自身的Ca 2+储存所包围的观察结果提出了这样的可能性，即核IP 3依赖的Ca 2+释放在ETC中起着关键作用。这提供了一种潜在的调节机制，该机制从ECC的全局胞质Ca 2+信号中局部和自主地起作用。此外，有证据表明：（i）肌浆网（SR）和NE是一个单一的连续Ca ~（2+）库，（ii）核孔复合体是Ca ~（2+）和大分子物质在胞质和核质之间通过的主要通道;（iii）NE的内膜宿主关键的Ca 2+处理蛋白，包括Na+/Ca 2+交换器（NCX）/GM 1复合物、兰尼碱受体（RyR），烟酸腺嘌呤二核苷酸磷酸受体（NAADPR）、Na+/K+ ATP酶和Na+/H+交换器。因此，似乎细胞核代表了一个Ca 2+信号传导结构域，该结构域配备有自己的离子通道和转运蛋白，允许复杂的局部Ca 2+信号。许多实验和建模方法已被用于细胞内Ca 2+信号的研究，但理解Ca 2+介导ECC和ECT的双重作用的关键在于细胞核和胞质区室中局部[Ca 2 +]的定量差异。在这篇综述中，我们讨论了关于不同类型的心脏细胞（成人心房和心室肌细胞）的核Ca 2+瞬变的起源和生理意义，以及实验和数学方法来研究Ca 2+和IP 3信号在细胞质和细胞核的知识状态。特别是，我们关注的概念是，高度定位的Ca 2+信号需要易位和激活Ca 2+依赖性转录因子（例如，活化T细胞的核因子，NFAT;组蛋白脱乙酰酶，HDAC）通过磷酸化/去磷酸化过程。
Calcium plays a crucial role in excitation-contraction coupling (ECC), but it is also a pivotal second messenger activating Ca2+-dependent transcription factors in a process termed excitation-transcription coupling (ETC). Evidence accumulated over the past decade indicates a pivotal role of inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release in the regulation of cytosolic and nuclear Ca2+ signals. IP3 is generated by stimulation of plasma membrane receptors that couple to phospholipase C (PLC), liberating IP3 from phosphatidylinositol 4,5-bisphosphate (PIP2). An intriguing aspect of IP3 signaling is the presence of the entire PIP2-PLC-IP3 signaling cascade as well as the presence of IP3Rs at the inner and outer membranes of the nuclear envelope (NE) which functions as a Ca2+ store. The observation that the nucleus is surrounded by its own putative Ca2+ store raises the possibility that nuclear IP3-dependent Ca2+ release plays a critical role in ETC. This provides a potential mechanism of regulation that acts locally and autonomously from the global cytosolic Ca2+ signal underlying ECC. Moreover, there is evidence that: (i) the sarcoplasmic reticulum (SR) and NE are a single contiguous Ca2+ store; (ii) the nuclear pore complex is the major gateway for Ca2+ and macromolecules to pass between the cytosol and the nucleoplasm; (iii) the inner membrane of the NE hosts key Ca2+ handling proteins including the Na+/Ca2+ exchanger (NCX)/GM1 complex, ryanodine receptors (RyRs), nicotinic acid adenine dinucleotide phosphate receptors (NAADPRs), Na+/K+ ATPase, and Na+/H+ exchanger. Thus, it appears that the nucleus represents a Ca2+ signaling domain equipped with its own ion channels and transporters that allow for complex local Ca2+ signals. Many experimental and modeling approaches have been used for the study of intracellular Ca2+ signaling but the key to the understanding of the dual role of Ca2+ mediating ECC and ECT lays in quantitative differences of local [Ca2+] in the nuclear and cytosolic compartment. In this review, we discuss the state of knowledge regarding the origin and the physiological implications of nuclear Ca2+ transients in different cardiac cell types (adult atrial and ventricular myocytes) as well as experimental and mathematical approaches to study Ca2+ and IP3 signaling in the cytosol and nucleus. In particular, we focus on the concept that highly localized Ca2+ signals are required to translocate and activate Ca2+-dependent transcription factors (e.g., nuclear factor of activated T-cells, NFAT; histone deacetylase, HDAC) through phosphorylation/dephosphorylation processes.
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影响因子：
3.7
作者：
Crossman DJ;Ruygrok PN;Soeller C;Cannell MB
通讯作者：
Cannell MB
DOI：
10.1073/pnas.89.20.9895
发表时间：
1992-10-15
影响因子：
11.1
作者：
DEYOUNG, GW;KEIZER, J
通讯作者：
KEIZER, J
影响因子：
20.1
作者：
Heinzel, FR;Bito, V;Sipido, KR
通讯作者：
Sipido, KR
影响因子：
3.4
作者：
Franzini-Armstrong, C;Protasi, F;Ramesh, V
通讯作者：
Ramesh, V
DOI：
10.1073/pnas.0905485106
发表时间：
2009-07-07
影响因子：
11.1
作者：
Harzheim, Dagmar;Movassagh, Mehregan;Roderick, H. Llewelyn
通讯作者：
Roderick, H. Llewelyn