Gating of cyclic nucleotide-gated channels is voltage dependent
Gating of cyclic nucleotide-gated channels is voltage dependent
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DOI：
10.1038/ncomms1972
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发表时间：
2012-07-01
影响因子：
16.6
通讯作者：
Torre, Vincent
中科院分区：
文献类型：
--
作者：
Marchesi, Arin;Mazzolini, Monica;Torre, Vincent
环核苷酸门控通道属于电压门控离子通道家族，但孔开放需要细胞内环核苷酸的存在。在饱和激动剂的存在下，环核苷酸门控通道门控是电压无关的，并且不知道为什么环核苷酸门控通道尽管具有S4型电压传感器但对电压不敏感。在这里，我们报告，在Li+，Na+和K+的存在下，野生型环核苷酸门控A1和天然环核苷酸门控通道的门控是电压无关的，而它们的门控是高度电压依赖性的Rb+，Cs+和有机阳离子的存在下。诱变实验表明，电压传感发生通过一个电压传感器组成的孔中的带电/极性残基和S4型电压传感器。在进化过程中，当Na+或K+渗透时，环核苷酸门控通道失去其电压敏感能力，使得脊椎动物感光细胞环核苷酸门控通道在负电压下打开，这是光转导的必要条件。
Cyclic nucleotide-gated channels belong to the family of voltage-gated ion channels, but pore opening requires the presence of intracellular cyclic nucleotides. In the presence of a saturating agonist, cyclic nucleotide-gated channel gating is voltage independent and it is not known why cyclic nucleotide-gated channels are voltage-insensitive despite harbouring the S4-type voltage sensor. Here we report that, in the presence of Li+, Na+ and K+, the gating of wild-type cyclic nucleotide-gated A1 and native cyclic nucleotide-gated channels is voltage independent, whereas their gating is highly voltage-dependent in the presence of Rb+, Cs+ and organic cations. Mutagenesis experiments show that voltage sensing occurs through a voltage sensor composed of charged/polar residues in the pore and of the S4-type voltage sensor. During evolution, cyclic nucleotide-gated channels lose their voltage-sensing ability when Na+ or K+ permeate so that the vertebrate photoreceptor cyclic nucleotide-gated channels are open at negative voltages, a necessary condition for phototransduction.