The permeation mechanism of organic cations through a CNG mimic channel

Luisa M. R. Napolitano, Arin Marchesi, Alex Rodriguez, Matteo De March, Silvia Onesti, Alessandro Laio, Vincent Torre

Abstract: Author summary Cyclic Nucleotide Gated (CNG) channels are nonselective cation channels with a key role in sensory transduction. Despite sharing a high homology with K+ channels, they allow the passage of large compounds like dimethylammonium (DMA) which are not permeable through K+ channels. We demonstrate that the conduction mechanism of this compound is radically different from the textbook scenario, in which an ion, in order to diffuse through the channel, must cross a series of barriers, whose height is possibly perturbed by the presence of other ions in the channel. We show that permeation of large cations in CNG is due to the destabilization of the pore induced by the simultaneous presence of two ions in the channel.