在心脏发生过程中肌动脉trpm7删除的时间可变地破坏成人心室功能,导电和再极化
Rajan Sah1, Pietro Mesirca, Xenos Mason
1Howard Hughes Medical Institute, Department of Cardiology, Manton Center for Orphan Disease, Children's Hospital Boston, 320 Longwood Ave, Enders 1309, Boston, MA 02115, USA.
Circulation
|June 5, 2013
概括
暂时受体潜力拉斯7 (TRPM7) 对于心脏早期发育至关重要. 在发育过程中TRPM7的损失导致心力衰竭,而成年人的心能容忍它的缺失.
科学领域:
- 心血管生物学 心血管生物学
- 离子通道生理学 离子通道生理学
- 发育生物学 发展生物学
背景情况:
- 短暂受体潜能 (TRP) 通道是具有多种生理作用的重要离子通道.
- TRPM7,一种双价透通道和激酶,与心房动有关,但其在心室肌肉中的作用尚不清楚.
- 之前的研究将其他TRP通道 (TRPC1,TRPC3,TRPC6) 与心脏缩和TRPM4突变与心脏阻塞联系起来.
研究的目的:
- 研究TRPM7在心室肌肉功能和发育中的作用.
- 为了确定TRPM7是否对正常的心脏发育和成人心室功能至关重要.
- 探索TRPM7删除在不同发展阶段的后果.
主要方法:
- 在各种发育时间点 (早期,中期,晚期) 中生成具有TRPM7删除的心脏向淘汰小鼠.
- 评估心脏功能,形态和生存在淘汰赛小鼠.
- 使用微阵列分析心肌转录形状.
- 电生理学研究,以评估动力潜力和离子电流.
主要成果:
- 早期删除TRPM7 (在胚胎第9天之前) 导致胚胎致死性,原因是紧心肌的低扩散.
- 晚期删除TRPM7 (大约13个胚胎日) 导致具有正常心室功能的活力成年小鼠.
- 在50%的小鼠中,中间删除导致心肌病,心脏阻塞和心律失常,与改变的基因表达相关 (例如,减少Hdac9,Kcnd2,Hcn4).
- 电生理学变化包括动作潜力的延长和短暂的外向电流 (Ito) 和起器电流 (If) 的减少.
结论:
- 在早期心脏发生过程中,TRPM7对心肌增殖至关重要.
- 在基底条件下,TRPM7在成年腹腔心肌中是不可用的.
- 在中期发育过程中TRPM7的损失会改变成人心肌转录特征,损害心室功能,导电和再极化.
更多相关视频
03:45Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
3.3K
09:36Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
Published on: December 22, 2023
2.0K
相关概念视频
01:28Mechanism of Cardiac Arrhythmias
2.8K
Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
2.8K
01:30Cardiac Action Potential
11.9K
Cardiac action potentials are essential for proper heart function, enabling the rhythmic contractions needed for adequate blood circulation. Nodal cells and Purkinje fibers, specialized for electrical conduction, generate these action potentials.
The cardiac action potential process involves a series of phases characterized by the movement of ions across the cardiac cell membranes, leading to the depolarization and repolarization of the cardiac myocytes.
Ionic Basis of Cardiac Action Potentials
The cardiac action potential process involves a series of phases characterized by the movement of ions across the cardiac cell membranes, leading to the depolarization and repolarization of the cardiac myocytes.
Ionic Basis of Cardiac Action Potentials
11.9K
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
810
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
810