Name
Abstract | ||
|---|---|---|
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels control electrical rhythmicity in specialized brain and heart cells. We quantitatively analysed voltage-dependent activation of homotetrameric HCN2 channels and its modulation by the second messenger cAMP using global fits of hidden Markovian models to complex experimental data. We show that voltage-dependent activation is essentially governed by two separable voltage-dependent steps followed by voltage-independent opening of the pore. According to this model analysis, the binding of cAMP to the channels exerts multiple effects on the voltage-dependent gating: It stabilizes the open pore, reduces the total gating charge from 8 to 5, makes an additional closed state outside the activation pathway accessible and strongly accelerates the ON-gating but not the OFF-gating. Furthermore, the open channel has a much slower computed OFF-gating current than the closed channel, in both the absence and presence of cAMP. Together, these results provide detailed new insight into the voltage- and cAMP-induced activation gating of HCN channels. |
Year | DOI | Venue |
|---|---|---|
2018 | 10.1371/journal.pcbi.1006045 | PLOS COMPUTATIONAL BIOLOGY |
Field | DocType | Volume |
Hyperpolarization (biology),Membrane potential,Gating,Biology,Biophysics,Heart cells,Communication channel,Modulation,Genetics,Second messenger system | Journal | 14 |
Issue | Citations | PageRank |
3 | 0 | 0.34 |
References | Authors | |
1 | 6 | |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Sabine Hummert | 1 | 0 | 0.34 |
| Susanne Thon | 2 | 0 | 0.34 |
| Thomas Eick | 3 | 0 | 0.68 |
| Ralf Schmauder | 4 | 0 | 0.34 |
| Eckhard Schulz | 5 | 1 | 0.96 |
| Klaus Benndorf | 6 | 1 | 0.96 |