Cardiac Pacemaker Dysfunction Arising From Different Studies of Ion Channel Remodeling in the Aging Rat Heart.
Cardiac Pacemaker Dysfunction Arising From Different Studies of Ion Channel Remodeling in the Aging Rat Heart.
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心脏起搏器功能障碍是由老化大鼠心脏中离子通道重塑的不同研究引起的。
DOI：
10.3389/fphys.2020.546508
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发表时间：
2020
影响因子：
4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Alghamdi AM;Boyett MR;Hancox JC;Zhang H
作为心脏起搏器的窦房结（SAN）的功能随着年龄的增长而下降，导致老年人窦房结功能障碍（SND）的发生率增加。本研究评估了年龄相关SND的潜在离子机制。两组研究发现老龄大鼠SAN中一些膜离子通道发生了复杂多样的变化，第一组（Aging Study-1）研究发现，老龄大鼠SAN中一些膜离子通道的mRNA表达发生了较大变化，Cav1.2、Cav1.3、KvLQT1、Kv4.2离子通道mRNA表达上调，SERCA2a Ca2+处理蛋白表达下调，Cav3.1、NCX、HCN1和RYR2 Ca2+时钟蛋白表达下调。第二组（Aging Study-2）显示出不同的变化模式，包括Cav1.2、Cav1.3、HCN4和RYR2的下调，NCX和SERCA密度和蛋白的增加。尽管两组数据在某些特定离子通道上有相似的发现，如HCN4、NCX和RYR2的下调，但在其他一些膜离子通道上却存在矛盾的变化，如老龄大鼠SAN中Cav1.2、NCX和SERCA2a的上调或下调。本研究旨在验证一个假设，即年龄相关的SND可能是由不同的离子和分子重塑模式引起的。为了验证这一假设，我们修改了大鼠SAN肌细胞动作电位的数学模型，以模拟老化研究1和老化研究2中观察到的年龄诱导的膜离子通道和细胞内Ca2+处理变化的功能影响。评估了两个数据集中每个单独重塑的离子通道和Ca2+处理的作用和相对重要性。基于Aging Study-1或Aging Study-2的研究表明，年龄诱导的离子通道和Ca2+处理的变化产生了类似的心动过缓效应，表现为心率（HR）的显著降低，这与实验观察相匹配。进一步的分析表明，尽管在这两项研究中SND是由所有离子通道重塑和Ca2+处理的综合作用引起的，但ICaL的变化发挥了最重要的影响。
The function of the sinoatrial node (SAN), the pacemaker of the heart, declines with age, resulting in increased incidence of sinoatrial node dysfunction (SND) in older adults. The present study assesses potential ionic mechanisms underlying age associated SND. Two group studies have identified complex and various changes in some of membrane ion channels in aged rat SAN, the first group (Aging Study-1) indicates a considerable changes of gene expression with up-regulation of mRNA in ion channels of Cav1.2, Cav1.3 and KvLQT1, Kv4.2, and the Ca2+ handling proteins of SERCA2a, and down-regulation of Cav3.1, NCX, and HCN1 and the Ca2+-clock proteins of RYR2. The second group (Aging Study-2) suggests a different pattern of changes, including down regulation of Cav1.2, Cav1.3 and HCN4, and RYR2, and an increase of NCX and SERCA densities and proteins. Although both data sets shared a similar finding for some specific ion channels, such as down regulation of HCN4, NCX, and RYR2, there are contradictory changes for some other membrane ion channels, such as either up-regulation or down-regulation of Cav1.2, NCX and SERCA2a in aged rat SAN. The present study aims to test a hypothesis that age-related SND may arise from different ionic and molecular remodeling patterns. To test this hypothesis, a mathematical model of the electrical action potential of rat SAN myocytes was modified to simulate the functional impact of age-induced changes on membrane ion channels and intracellular Ca2+ handling as observed in Aging Study-1 and Aging Study-2. The role and relative importance of each individually remodeled ion channels and Ca2+-handling in the two datasets were evaluated. It was shown that the age-induced changes in ion channels and Ca2+-handling, based on either Aging Study-1 or Aging Study-2, produced similar bradycardic effects as manifested by a marked reduction in the heart rate (HR) that matched experimental observations. Further analysis showed that although the SND arose from an integrated action of all remodeling of ion channels and Ca2+-handling in both studies, it was the change to ICaL that played the most important influence.
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DOI：
10.1152/physiologyonline.2002.17.1.32
发表时间：
2002-02-01
期刊：
NEWS IN PHYSIOLOGICAL SCIENCES
影响因子：
--
作者：
Accili, EA;Proenza, C;DiFrancesco, D
通讯作者：
DiFrancesco, D
DOI：
10.1113/jp276508
发表时间：
2018-12
期刊：
The Journal of physiology
影响因子：
--
作者：
Choudhury M;Black N;Alghamdi A;D'Souza A;Wang R;Yanni J;Dobrzynski H;Kingston PA;Zhang H;Boyett MR;Morris GM
通讯作者：
Morris GM
影响因子：
5.5
作者：
HAGIWARA, N;IRISAWA, H;KAMEYAMA, M
通讯作者：
KAMEYAMA, M
影响因子：
3
作者：
Choudhury, Moinuddin;Boyett, Mark R.;Morris, Gwilym M.
通讯作者：
Morris, Gwilym M.
影响因子：
37.8
作者：
Jones, Sandra A.;Boyett, Mark R.;Lancaster, Matthew K.
通讯作者：
Lancaster, Matthew K.