Inner activation gate in S6 contributes to the state-dependent binding of cAMP in full-length HCN2 channel.

ABSTRACT: Recently, applications of the patch-clamp fluorometry (PCF) technique in studies of cyclic nucleotide-gated (CNG) and hyperpolarization-activated, cyclic nucleotide-regulated (HCN) channels have provided direct evidence for the long-held notion that ligands preferably bind to and stabilize these channels in an open state. This state-dependent ligand-channel interaction involves contributions from not only the ligand-binding domain but also other discrete structural elements within the channel protein. This insight led us to investigate whether the pore of the HCN channel plays a role in the ligand-whole channel interaction. We used three well-characterized HCN channel blockers to probe the ion-conducting passage. The PCF technique was used to simultaneously monitor channel activity and cAM

SUBMITTER: Wu S 

PROVIDER: S-EPMC3382721 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature