慢性人类心房的L型Ca2+电流下调与蛋白质酸酶的活性增加有关
1Department of Pharmacology,Dresden University of Technology, Dresden, Germany.
Circulation
|October 20, 2004
概括
在心房 (AF) 中,降低L型Ca2+电流 (I(Ca,L)) 与增加的蛋白质酸酶活性有关. 这表明蛋白酸酶是治疗AF的潜在治疗点.
科学领域:
- 心血管生理学心血管生理学
- 分子心脏病学分子心脏病学
- 电力生理学 电力生理学
背景情况:
- 下调L型Ca2+电流 (I(Ca,L)) 是心房动 (AF) 电气改造的一个关键因素.
- 在AF中降低I ((Ca,L) 的精确分子机制仍然不完全理解.
- 这项研究研究了酸化依赖性通道调节在AF相关的I(Ca,L) 减少中的作用.
研究的目的:
- 为了确定慢性AF中的降低I ((Ca,L) 是否与酸化依赖的通道调节的改变有关.
- 研究蛋白激酶和酸酶对AF中I (Ca,L) 调节的贡献.
主要方法:
- 采用全细胞电压技术,测量心房肌细胞中的I ((Ca,L)).
- 生物化学测试被用来评估蛋白质水平和调节酶的活性.
- 研究对有鼻节律 (SR) 和慢性AF的患者的心房组织和肌细胞进行了研究.
主要成果:
- 与SR患者相比,AF患者的基础I (Ca,L) 显著较小.
- 在AF和SR组之间,关键的I(Ca,L) 通道子单元 (alpha1c,beta2a) 的蛋白质含量没有差异.
- 在AF中观察到蛋白酸酶2A活性和表达的增加,有助于基底I (Ca,L) 的受损.
结论:
- 在AF中蛋白酸酶活性增加直接导致基底I (Ca,L) 的损害.
- 蛋白酸酶代表了对心房的管理潜在的治疗点.
- 了解这些分子机制对于开发新的AF治疗方法至关重要.
更多相关视频
10:53Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
06:22Isolation of High Quality Murine Atrial and Ventricular Myocytes for Simultaneous Measurements of Ca2+ Transients and L-Type Calcium Current
Published on: November 3, 2020
相关概念视频
01:34ATP Driven Pumps II: P-type Pumps
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
01:21G-Protein Gated Ion Channels
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 organs,...
Sensory organs,...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers
Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
01:20Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
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...
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...