Probability fluxes and transition paths in a Markovian model describing complex subunit cooperativity in HCN2 channels.

ABSTRACT: Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are voltage-gated tetrameric cation channels that generate electrical rhythmicity in neurons and cardiomyocytes. Activation can be enhanced by the binding of adenosine-3',5'-cyclic monophosphate (cAMP) to an intracellular cyclic nucleotide binding domain. Based on previously determined rate constants for a complex Markovian model describing the gating of homotetrameric HCN2 channels, we analyzed probability fluxes within this model, including unidirectional probability fluxes and the probability flux along transition paths. The time-dependent probability fluxes quantify the contributions of all 13 transitions of the model to channel activation. The binding of the first, third and fourth ligand evoked robust channel open

SUBMITTER: Benndorf K 

PROVIDER: S-EPMC3475657 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature