Autonomic regulation of voltage-gated cardiac ion channels.

Autonomic regulation of voltage-gated cardiac ion channels.
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DOI:
10.1111/j.1540-8167.2006.00387.x
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发表时间:
2006-05-01
影响因子:
2.7
通讯作者:
Butters, Carol A
Butters, Carol A
中科院分区:
医学3区
文献类型:
--
作者:
Shibata, Erwin F;Brown, Tracy L Y;Butters, Carol A

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改变电压门控离子通道电流,通过改变通道数目或电压依赖的动力学,调节动作电位沿着单个细胞的质膜以及从一个细胞到其相邻细胞的传播。心肌肌膜钠通道(Na(V)1.5)数量的功能性增加是通过β肾上腺素刺激的G蛋白调节小窝来实现的。我们发现Na(V)1.5、Ca(V)1.2a和K(V)1.5通道特异性地定位于离体腔泡膜,并定位于用小窝蛋白-3标记的肌膜区域。此外,我们还发现,Na(V)1.5、Ca(V)1.2a和K(V)1.5通道抗体标记的是分离的小窝的相同亚群。质膜分析表明,Na(V)1.5、Ca(V)1.2a和K(V)1.5与小窝蛋白-3形成簇。这可能对肾上腺素能通路改变心脏动作电位形态和兴奋性波速度的方式有有趣的影响。
Altering voltage-gated ion channel currents, by changing channel number or voltage-dependent kinetics, regulates the propagation of action potentials along the plasma membrane of individual cells and from one cell to its neighbors. Functional increases in the number of cardiac sodium channels (Na(V)1.5) at the myocardial sarcolemma are accomplished by the regulation of caveolae by beta adrenergically stimulated G-proteins. We demonstrate that Na(V)1.5, Ca(V)1.2a, and K(V)1.5 channels specifically localize to isolated caveolar membranes, and to punctate regions of the sarcolemma labeled with caveolin-3. In addition, we show that Na(V)1.5, Ca(V)1.2a, and K(V)1.5 channel antibodies label the same subpopulation of isolated caveolae. Plasma membrane sheet assays demonstrate that Na(V)1.5, Ca(V)1.2a, and K(V)1.5 cluster with caveolin-3. This may have interesting implications for the way in which adrenergic pathways alter the cardiac action potential morphology and the velocity of the excitatory wave.