Nanoscale Organization, Regulation, and Dynamic Reorganization of Cardiac Calcium Channels.
Nanoscale Organization, Regulation, and Dynamic Reorganization of Cardiac Calcium Channels.
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DOI：
10.3389/fphys.2021.810408
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发表时间：
2021
影响因子：
4
通讯作者：
Dixon RE
中科院分区：
文献类型：
--
作者：
Dixon RE
心肌细胞的结构特化和靶向递送途径确保L型Ca 2+通道（CaV1.2）集中在t-小管肌膜上，其细胞内伴侣2型兰尼碱受体（RyR 2）聚集在连接肌浆网（jSR）上。这两组心脏钙通道簇的组织和分布是心肌均匀收缩的关键基础。在这两组相邻簇之间的Ca 2+信号传导产生Ca 2+火花，其在健康情况下不能升级为Ca 2+波，因为相邻簇有足够的分离，使得从一个RyR 2簇或超簇释放Ca 2+不能激活和维持从相邻簇释放Ca 2+。相反，成千上万的这些Ca 2+释放单位（CRU）在动作电位期间产生几乎同时的Ca 2+火花，当钙诱导的钙释放从RyR 2被去极化诱导的Ca 2+内流通过电压依赖性CaV1.2通道簇刺激时。这些火花相加以产生激活肌丝的全局Ca 2+瞬变，并且因此动作电位的电信号被转换成功能输出，心肌收缩。为了产生更多或更少的收缩力以匹配身体的血液动力学和代谢需求，心脏通过改变钙通道的活性以相应地调节兴奋-收缩偶联来响应β-肾上腺素能信号传导。最近积累的证据表明，这种调谐过程还涉及改变表达，并在各自的膜上动态重组CaV1.2和RyR 2通道，以控制Ca 2+进入的幅度，SR Ca 2+释放和心肌功能。在心力衰竭和衰老中，这些关键Ca 2+信号蛋白的分布和重组改变与结构重塑一起发生，并被认为有助于收缩功能受损。在本次审查中，我们讨论这些最新的发展，其影响，以及未来的问题要解决。
The architectural specializations and targeted delivery pathways of cardiomyocytes ensure that L-type Ca2+ channels (CaV1.2) are concentrated on the t-tubule sarcolemma within nanometers of their intracellular partners the type 2 ryanodine receptors (RyR2) which cluster on the junctional sarcoplasmic reticulum (jSR). The organization and distribution of these two groups of cardiac calcium channel clusters critically underlies the uniform contraction of the myocardium. Ca2+ signaling between these two sets of adjacent clusters produces Ca2+ sparks that in health, cannot escalate into Ca2+ waves because there is sufficient separation of adjacent clusters so that the release of Ca2+ from one RyR2 cluster or supercluster, cannot activate and sustain the release of Ca2+ from neighboring clusters. Instead, thousands of these Ca2+ release units (CRUs) generate near simultaneous Ca2+ sparks across every cardiomyocyte during the action potential when calcium induced calcium release from RyR2 is stimulated by depolarization induced Ca2+ influx through voltage dependent CaV1.2 channel clusters. These sparks summate to generate a global Ca2+ transient that activates the myofilaments and thus the electrical signal of the action potential is transduced into a functional output, myocardial contraction. To generate more, or less contractile force to match the hemodynamic and metabolic demands of the body, the heart responds to β-adrenergic signaling by altering activity of calcium channels to tune excitation-contraction coupling accordingly. Recent accumulating evidence suggests that this tuning process also involves altered expression, and dynamic reorganization of CaV1.2 and RyR2 channels on their respective membranes to control the amplitude of Ca2+ entry, SR Ca2+ release and myocardial function. In heart failure and aging, altered distribution and reorganization of these key Ca2+ signaling proteins occurs alongside architectural remodeling and is thought to contribute to impaired contractile function. In the present review we discuss these latest developments, their implications, and future questions to be addressed.
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影响因子：
4
作者：
Benitah JP;Perrier R;Mercadier JJ;Pereira L;Gómez AM
通讯作者：
Gómez AM
DOI：
10.1126/science.aag1417
发表时间：
2017-03-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Castellano BM;Thelen AM;Moldavski O;Feltes M;van der Welle RE;Mydock-McGrane L;Jiang X;van Eijkeren RJ;Davis OB;Louie SM;Perera RM;Covey DF;Nomura DK;Ory DS;Zoncu R
通讯作者：
Zoncu R
影响因子：
56.9
作者：
Balzarotti, Francisco;Eilers, Yvan;Hell, Stefan W.
通讯作者：
Hell, Stefan W.
影响因子：
10.8
作者：
Balijepalli, RC;Lokuta, AJ;Kamp, TJ
通讯作者：
Kamp, TJ
DOI：
10.1152/ajpheart.00209.2018
发表时间：
2018-11-01
影响因子：
4.8
作者：
Bryant, Simon M.;Kong, Cherrie H. T.;Orchard, Clive H.
通讯作者：
Orchard, Clive H.