Alkali metal cations modulate the geometry of different binding sites in HCN4 selectivity filter for permeation or block.

ABSTRACT: Hyperpolarization-activated cyclic-nucleotide gated (HCN) channels are important for timing biological processes like heartbeat and neuronal firing. Their weak cation selectivity is determined by a filter domain with only two binding sites for K+ and one for Na+. The latter acts as a weak blocker, which is released in combination with a dynamic widening of the filter by K+ ions, giving rise to a mixed K+/Na+ current. Here, we apply molecular dynamics simulations to systematically investigate the interactions of five alkali metal cations with the filter of the open HCN4 pore. Simulations recapitulate experimental data like a low Li+ permeability, considerable Rb+ conductance, a block by Cs+ as well as a punch through of Cs+ ions at high negative voltages. Differential binding of the cation

SUBMITTER: Krumbach JH 

PROVIDER: S-EPMC10386491 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature