Voltage-sensing mechanism is conserved among ion channels gated by opposite voltages
Voltage-sensing mechanism is conserved among ion channels gated by opposite voltages
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DOI：
10.1038/nature01038
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发表时间：
2002-10-24
期刊：
影响因子：
64.8
通讯作者：
Larsson, HP
中科院分区：
文献类型：
--
作者：
Männikkö, R;Elinder, F;Larsson, HP
超极化激活的环核苷酸门控(HCN)离子通道在大脑和心脏的节律性放电细胞中被发现(1)，其中通过HCN通道的阳离子电流(称为i-h或i-f)导致这些细胞重复放电(2)。这些通道也存在于非起搏细胞中，它们控制静息膜特性，调节突触传递，调节长时程增强，并限制极端超极化(3-7)。HCN通道与去极化激活钾(Kv)通道具有相同的序列基序，如第四跨膜片段S4(8，9)。S4是Kv通道的主要电压传感器，其中S4电荷的跨膜运动触发激活门(10-17)的打开。在这里，我们使用半胱氨酸可及性方法(10-12)，研究S4是否在HCN通道中运动。我们发现S4运动在Kv和Hcn通道之间是保守的，这表明S4也是Hcn通道中的电压传感器。我们的结果表明，在相对电压门控的Kv和Hcn通道中，存在一种保守的电压敏感机制，但在这两种不同的通道中，电压传感器与激活门之间存在不同的耦合机制。
Hyperpolarization-activated cyclic-nucleotide-gated (HCN) ion channels are found in rhythmically firing cells in the brain and in the heart(1), where the cation current through HCN channels (called I-h or I-f) causes these cells to fire repeatedly(2). These channels are also found in non-pacing cells, where they control resting membrane properties, modulate synaptic transmission, mediate long-term potentiation, and limit extreme hyperpolarizations(3-7). HCN channels share sequence motifs with depolarization-activated potassium (Kv) channels, such as the fourth transmembrane segment S4(8,9). S4 is the main voltage sensor of Kv channels, in which transmembrane movement of S4 charges triggers the opening of the activation gate(10-17). Here, using cysteine accessibility methods(10-12), we investigate whether S4 moves in an HCN channel. We show that S4 movement is conserved between Kv and HCN channels, which indicates that S4 is also the voltage sensor in HCN channels. Our results suggest that a conserved voltage-sensing mechanism operates in the oppositely voltage-gated Kv and HCN channels, but that there are different coupling mechanisms between the voltage sensor and activation gate in the two different channels.