Channelpedia

PubMed 22084239


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: HCN1 , HCN2 , HCN3 , HCN4



Title: Energetics of cyclic AMP binding to HCN channel C terminus reveal negative cooperativity.

Authors: Sarah S Chow, Filip Van Petegem, Eric A Accili

Journal, date & volume: J. Biol. Chem., 2012 Jan 2 , 287, 600-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22084239


Abstract
Cyclic AMP binds to the HCN channel C terminus and variably stabilizes its open state. Using isothermal titration calorimetry, we show that cAMP binds to one subunit of tetrameric HCN2 and HCN4 C termini with high affinity (∼0.12 μM) and subsequently with low affinity (∼1 μM) to the remaining three subunits. Changes induced by high affinity binding already exist in both a constrained HCN2 tetramer and the unconstrained HCN1 tetramer. Natural "preactivation" of HCN1 may explain both the smaller effect of cAMP on stabilizing its open state and the opening of unliganded HCN1, which occurs as though already disinhibited.