相关实验视频
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Measuring Fast Calcium Fluxes in Cardiomyocytes
Published on: November 29, 2011
心脏电流的交感调节完全是由于cAMP依赖的酸化
H C Hartzell1, P F Méry, R Fischmeister
1Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322.
Nature
|June 13, 1991
概括
同情神经系统的同情神经系统.
科学领域:
- 心脏病学 心脏病学
- 分子药理学分子药理学
- 细胞生理学 细胞生理学
背景情况:
- 交感神经系统的刺激通过增强的电压导电电流 (ICa) 增加了心脏收缩性.
- 这种效应传统上归因于β-上腺素受体激活和循环AMP (cAMP) 依存蛋白激酶A (PKA) 通道的酸化.
- 另一个假设提出了一个直接的,膜界限的G蛋白通路,用于快速的ICa调节.
研究的目的:
- 研究直接G蛋白通路与cAMP依赖酸化在心脏ICa的β-上腺刺激中的作用.
- 确定交感神经系统对心脏收缩能力的积极内效应背后的机制.
主要方法:
- 全细胞补丁电生理学被用来测量隔离的青,大鼠和几内亚猪心室肌细胞中的ICa.
- 实验涉及使用β-上腺素激动剂异二醇进行刺激.
- 评估了cAMP依赖的酸化抑制剂的影响,ICa变化与收缩力测量相关.
主要成果:
- 在所有测试物种中,异二醇诱导了ICa的缓慢,单相增加.
- 这种增加被cAMP依赖酸化的抑制剂完全取消.
- ICa升高的时间过程反映了心脏收缩力的增加.
结论:
- 交感神经系统对心脏ICa的调节完全由cAMP依赖的酸化介导.
- 这些发现驳斥了在心室肌细胞中进行ICa刺激的直接,膜界限的G蛋白通路的存在.
- 结果澄清了控制心脏收缩的同情控制的分子机制.
相关概念视频
G-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,...
cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Calmodulin-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,...
Relaxation of Skeletal Muscles
The period of muscle contraction primarily influences the duration of stimulation at the neuromuscular junction (NMJ), the presence of free calcium ions in the sarcoplasm, and the availability of energy or ATP to support contractions.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open.
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open.
Smooth Muscle Contraction
Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...

