Weak Cation Selectivity in HCN Channels Results From K⁺-Mediated Release of Na⁺ From Selectivity Filter Binding Sites.

ABSTRACT: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate the pacemaker current which plays an important role in the timing of various biological processes like the heart beat. We used umbrella sampling to explore the potential of mean force for the conduction of potassium and sodium through the open HCN4 pore. Our data explain distinct functional features like low unitary conductance and weak selectivity as a result of high energetic barriers inside the selectivity filter of this channel. They exceed the 3-5 kJ/mol threshold which is presumed as maximal barrier for diffusion-limited conductance. Furthermore, simulations provide a thermodynamic explanation for the weak cation selectivity of HCN channels that contain only two ion binding sites in the selectivity filter (SF

SUBMITTER: Bauer D 

PROVIDER: S-EPMC9492253 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature