CAMP binding to closed pacemaker ion channels is non-cooperative.

ABSTRACT: Electrical activity in the brain and heart depends on rhythmic generation of action potentials by pacemaker ion channels (HCN) whose activity is regulated by cAMP binding¹. Previous work has uncovered evidence for both positive and negative cooperativity in cAMP binding^2,3, but such bulk measurements suffer from limited parameter resolution. Efforts to eliminate this ambiguity using single-molecule techniques have been hampered by the inability to directly monitor binding of individual ligand molecules to membrane receptors at physiological concentrations. Here we overcome these challenges using nanophotonic zero-mode waveguides⁴ to directly resolve binding dynamics of individual ligands to multimeric HCN1 and HCN2 ion channels. We show that cAMP binds inde

SUBMITTER: White DS 

PROVIDER: S-EPMC8513821 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature