Uncoupling of Voltage- and Ligand-Induced Activation in HCN2 Channels by Glycine Inserts.

ABSTRACT: Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are tetramers that generate electrical rhythmicity in special brain neurons and cardiomyocytes. The channels are activated by membrane hyperpolarization. The binding of cAMP to the four available cyclic nucleotide-binding domains (CNBD) enhances channel activation. We analyzed in the present study the mechanism of how the effect of cAMP binding is transmitted to the pore domain. Our strategy was to uncouple the C-linker (CL) from the channel core by inserting one to five glycine residues between the S6 gate and the A'-helix (constructs 1G to 5G). We quantified in full-length HCN2 channels the resulting functional effects of the inserted glycines by current activation as well as the structural dynamics and statics using

SUBMITTER: Yuksel S 

PROVIDER: S-EPMC9452628 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature