暂时的受体潜力在心房动中依赖3通道的纤维细胞调节
Masahide Harada1, Xiaobin Luo, Xiao Yan Qi
1Department of Medicine and Research Center, Montreal Heart Institute and Universite´ de Montre´al, Montreal, Quebec, Canada.
Circulation
|September 21, 2012
概括
暂时受体潜在的正规-3 (TRPC3) 通道驱动心脏纤维细胞激活在心房动 (AF). 在狗模型中,用Pyrazole-3阻断TRPC3通道在体内抑制了AF,并防止了疾病的进展.
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
- 心房动病理生理学
背景情况:
- 纤维细胞增殖和分化是心房动 (AF) 中心房重塑的关键.
- 暂时受体潜在的正规-3 (TRPC3) 通道正在研究它们在调节心脏纤维细胞中的作用.
研究的目的:
- 研究Ca(2+) 透的TRPC3通道在调节心脏纤维细胞活动中的作用.
- 确定TRPC3通道是否是AF的潜在治疗点.
主要方法:
- 使用新鲜分离的老鼠和狗心脏纤维细胞.
- 使用TRPC3通道阻断剂pyrazole-3和短发针RNA (shRNA) 进行TRPC3敲击.
- 评估的Ca2+) 流入,增殖,α-平滑肌肉的动蛋白表达,以及细胞外信号调节激酶 (ERK) 酸化.
- 从AF患者和动物模型中分析了心房中的TRPC3表达.
- 研究了微RNA-26和NFAT信号在TRPC3调控中的作用.
- 在AF的狗模型中体内给予pyrazole-3.
主要成果:
- 在心脏纤维细胞中检测到TRPC3通道和相关的离子电流.
- 皮拉-3抑制了血管新素II诱导的纤维细胞Ca(2+) 流入,增殖和α-平滑肌肉的动蛋白表达.
- 阻断TRPC3和去除Ca2+) 抑制了ERK的酸化,减少了纤维细胞的增殖.
- 来自患者和动物模型的AF心房中的TRPC3表达被上调.
- TRPC3敲击降低了狗心房纤维细胞的扩散.
- 微RNA-26在AF心房下调,导致TRPC3通过NFAT上调.
- 在体内给予Pyrazole-3抑制了AF,并减少了纤维细胞增殖和细胞外基因表达.
结论:
- TRPC3通道通过控制Ca2+) 流入和激活ERK信号来调节心脏纤维细胞的增殖和分化.
- AF通过NFAT介导的微RNA-26下调促进TRPC3通道表达,增强纤维细胞活性.
- 阻断TRPC3是一种潜在的治疗策略,正如其在预防AF基质在狗模型中的有效性所证明的那样.
相关概念视频
G-Protein Gated Ion Channels
7.2K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
7.2K
Intracellular Signaling Affects Focal Adhesions
3.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
3.8K
Mechanism of Cardiac Arrhythmias
2.7K
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.
2.7K
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
3.0K
Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
3.0K
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
2.7K
Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
2.7K


