SISSA (International School for Advanced Studies), Neurobiology Sector, via Bonomea 265, 34136 Trieste, Italy.
Nat Commun. 2012 Jul 24;3:973. doi: 10.1038/ncomms1972.
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.
环核苷酸门控通道属于电压门控离子通道家族，但孔道的开启需要细胞内环核苷酸的存在。在饱和激动剂存在的情况下，环核苷酸门控通道的门控与电压无关，尽管环核苷酸门控通道含有 S4 型电压传感器，但不知道为什么它们对电压不敏感。在这里，我们报告说，在存在 Li(+)、Na(+)和 K(+)的情况下，野生型环核苷酸门控 A1 和天然环核苷酸门控通道的门控与电压无关，而在存在 Rb(+)、Cs(+)和有机阳离子的情况下，其门控对电压高度依赖。突变实验表明，电压感应通过位于孔道中的带电荷/极性残基和 S4 型电压传感器的电压传感器发生。在进化过程中，当 Na(+)或 K(+)通透时，环核苷酸门控通道会失去其电压感应能力，因此脊椎动物光感受器环核苷酸门控通道在负电压下开放，这是光转导的必要条件。
