Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.
Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.
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DOI：
10.3389/fphys.2017.00043
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发表时间：
2017
影响因子：
4
通讯作者：
Liin SI
中科院分区：
文献类型：
--
作者：
Elinder F;Liin SI
多不饱和脂肪酸(PUFAs)作用于大多数离子通道，具有重要的生理和药理作用。本文综述了电压门控离子通道上大量多不饱和脂肪酸的数据，包括电压门控钠(NAV)、钾(KV)、钙(Cav)和质子(HV)通道，以及钙激活钾(KCA)和瞬时受体电位(Trp)通道。脂肪酸的一些影响似乎是通道特有的，而另一些似乎更普遍。脂肪酸作用于离子通道的共同特征是至少有两个顺式构型的双键和一个带电的羧基。我们总共为多不饱和脂肪酸确定和标记了五个不同的地点。多不饱和脂肪酸部位1：细胞内腔。多不饱和脂肪酸的结合降低了电流，有时作为时间依赖的阻断，导致明显的失活。多不饱和脂肪酸部位2：毛孔的胞外入口。绑定通向通道的阻塞。多不饱和脂肪酸位点3：细胞内门。绑定到这个位置可能会弯曲栅极打开并增加电流。多不饱和脂肪酸位点4：脂质双层的细胞外叶和电压敏感结构域之间的界面。通过带负电荷的多不饱和脂肪酸和带正电荷的电压传感器之间的静电吸引，结合到这个位点导致通道的打开。多不饱和脂肪酸位点5：脂双层细胞外小叶和孔域之间的界面。绑定到此站点会影响缓慢的失活。这种多不饱和脂肪酸功能位点的图谱可以形成电压门控离子通道的生理和药物修饰的基础。
Polyunsaturated fatty acids (PUFAs) act on most ion channels, thereby having significant physiological and pharmacological effects. In this review we summarize data from numerous PUFAs on voltage-gated ion channels containing one or several voltage-sensor domains, such as voltage-gated sodium (NaV), potassium (KV), calcium (CaV), and proton (HV) channels, as well as calcium-activated potassium (KCa), and transient receptor potential (TRP) channels. Some effects of fatty acids appear to be channel specific, whereas others seem to be more general. Common features for the fatty acids to act on the ion channels are at least two double bonds in cis geometry and a charged carboxyl group. In total we identify and label five different sites for the PUFAs. PUFA site 1: The intracellular cavity. Binding of PUFA reduces the current, sometimes as a time-dependent block, inducing an apparent inactivation. PUFA site 2: The extracellular entrance to the pore. Binding leads to a block of the channel. PUFA site 3: The intracellular gate. Binding to this site can bend the gate open and increase the current. PUFA site 4: The interface between the extracellular leaflet of the lipid bilayer and the voltage-sensor domain. Binding to this site leads to an opening of the channel via an electrostatic attraction between the negatively charged PUFA and the positively charged voltage sensor. PUFA site 5: The interface between the extracellular leaflet of the lipid bilayer and the pore domain. Binding to this site affects slow inactivation. This mapping of functional PUFA sites can form the basis for physiological and pharmacological modifications of voltage-gated ion channels.
影响因子：
2.4
作者：
Guo D;Xiang W;Seebahn A;Becker CM;Strauss O
通讯作者：
Strauss O
DOI：
10.1085/jgp.201311100
发表时间：
2013-11
期刊：
The Journal of general physiology
影响因子：
--
作者：
Latorre R;Contreras G
通讯作者：
Contreras G