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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249114 | PMC |
| http://dx.doi.org/10.1074/jbc.M111.269563 | DOI Listing |
Publication Analysis
Top Keywords
cyclic amp
8
hcn channel
8
channel terminus
8
open state
8
high affinity
8
energetics cyclic
4
amp binding
4
binding hcn
4
terminus reveal
4
reveal negative
4
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!