Marchesi 2012

2012 - Nature Communications 2012, 3, art. 973

Gating of CNG channels is voltage dependent

Marchesi A, Mazzolini M, Torre V.

Abstract:

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.

 

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