The Role of the L-Type Ca2+ Channel in Altered Metabolic Activity in a Murine Model of Hypertrophic Cardiomyopathy

心肌细胞 内科学 肥厚性心肌病 内分泌学 心肌病 生物 肌肉肥大 线粒体 细胞生物学 医学 心力衰竭
作者
Helena M. Viola,Victoria Johnstone,Henrietta Cserné Szappanos,Tara R. Richman,Tatiana Tsoutsman,Aleksandra Filipovska,Christopher Semsarian,Jonathan G. Seidman,Christine E. Seidman,Livia C. Hool
出处
期刊:JACC: Basic to Translational Science [Elsevier]
卷期号:1 (1-2): 61-72 被引量:13
标识
DOI:10.1016/j.jacbts.2015.12.001
摘要

Heterozygous mice (αMHC403/+ ) expressing the human disease-causing mutation Arg403Gln exhibit cardinal features of hypertrophic cardiomyopathy (HCM) including hypertrophy, myocyte disarray, and increased myocardial fibrosis. Treatment of αMHC403/+ mice with the L-type calcium channel (ICa-L) antagonist diltiazem has been shown to decrease left ventricular anterior wall thickness, cardiac myocyte hypertrophy, disarray, and fibrosis. However, the role of the ICa-L in the development of HCM is not known. In addition to maintaining cardiac excitation and contraction in myocytes, the ICa-L also regulates mitochondrial function through transmission of movement of ICa-L via cytoskeletal proteins to mitochondrial voltage-dependent anion channel. Here, the authors investigated the role of ICa-L in regulating mitochondrial function in αMHC403/+ mice. Whole-cell patch clamp studies showed that ICa-L current inactivation kinetics were significantly increased in αMHC403/+ cardiac myocytes, but that current density and channel expression were similar to wild-type cardiac myocytes. Activation of ICa-L caused a significantly greater increase in mitochondrial membrane potential and metabolic activity in αMHC403/+ . These increases were attenuated with ICa-L antagonists and following F-actin or β-tubulin depolymerization. The authors observed increased levels of fibroblast growth factor-21 in αMHC403/+ mice, and altered mitochondrial DNA copy number consistent with altered mitochondrial activity and the development of cardiomyopathy. These studies suggest that the Arg403Gln mutation leads to altered functional communication between ICa-L and mitochondria that is associated with increased metabolic activity, which may contribute to the development of cardiomyopathy. ICa-L antagonists may be effective in reducing the cardiomyopathy in HCM by altering metabolic activity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
刚刚
隐形曼青应助fairy采纳,获得10
1秒前
XiaoDai完成签到,获得积分10
1秒前
夏夏完成签到,获得积分20
2秒前
科研通AI5应助超级尔白采纳,获得10
2秒前
孙伟健发布了新的文献求助10
3秒前
3秒前
赫尔发布了新的文献求助20
3秒前
3秒前
邓佳鑫Alan应助MC大大怪采纳,获得10
4秒前
Selenge发布了新的文献求助10
4秒前
4秒前
4秒前
5秒前
圣城余晖发布了新的文献求助20
5秒前
rae发布了新的文献求助10
5秒前
5秒前
7秒前
7秒前
8秒前
9秒前
FashionBoy应助111采纳,获得10
9秒前
打打应助研友_8Y26PL采纳,获得10
10秒前
Lin发布了新的文献求助10
10秒前
不展发布了新的文献求助10
11秒前
11秒前
起承转合发布了新的文献求助10
11秒前
LSJ发布了新的文献求助10
11秒前
CcC关注了科研通微信公众号
12秒前
安生完成签到 ,获得积分10
13秒前
Hua发布了新的文献求助10
14秒前
舒服的牛排完成签到,获得积分10
14秒前
14秒前
14秒前
毛爱民完成签到,获得积分10
14秒前
15秒前
15秒前
16秒前
mzry发布了新的文献求助10
16秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Mechanistic Modeling of Gas-Liquid Two-Phase Flow in Pipes 2500
Kelsen’s Legacy: Legal Normativity, International Law and Democracy 1000
Handbook on Inequality and Social Capital 800
Conference Record, IAS Annual Meeting 1977 610
Interest Rate Modeling. Volume 3: Products and Risk Management 600
Interest Rate Modeling. Volume 2: Term Structure Models 600
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3546815
求助须知:如何正确求助?哪些是违规求助? 3123829
关于积分的说明 9357111
捐赠科研通 2822447
什么是DOI,文献DOI怎么找? 1551477
邀请新用户注册赠送积分活动 723475
科研通“疑难数据库(出版商)”最低求助积分说明 713766