List of PDB codes for currently available structures of HCN channel isoforms
| Isoform . | PDB code . | State . | Muta-tions . | Ligand/Blocker/Modulator . | Modeled/total residues . | Resolu-tion (Å) . | Organism . | Deposition author/s . | Released . |
|---|---|---|---|---|---|---|---|---|---|
| HCN1 | 5U6O | Voltage sensors in up configuration Closed pore | None | None | 482/660 | 3.5 | H. sapiens | Lee et al. | 2017-01-25 |
| HCN1 | 5U6P | Voltage sensors in up configuration Closed pore | None | cAMP | 504/660 | 3.51 | H. sapiens | Lee et al. | 2017-01-25 |
| HCN1 | 6UQF | Voltage sensors in down configuration Closed pore | F186C S264C | cAMP | 531/660 | 3.04 | H. sapiens | Lee et al. | 2019-12-11 |
| HCN1 | 6UQG | Voltage sensors in up configuration Closed pore | Y289D | cAMP | 530/660 | 3.54 | H. sapiens | Lee et al. | 2019-12-11 |
| HCN1 | 8T4M | Voltage sensors in up configuration Closed pore | F186C S264C | cAMP | 533/890 | 3.16 | H. sapiens | Burtscher et al. | 2024-06-12 |
| HCN1 | 8T4Y | Voltage sensors Intermediate configuration Closed pore | F186C S264C C309A | cAMP | 501/890 | 3.58 | H. sapiens | Burtscher et al. | 2024-06-19 |
| HCN1 | 8T50 | Voltage sensors in down configuration Open pore conductive | F186C S264C | cAMP | 474/890 | 3.6 | H. sapiens | Burtscher et al. | 2024-07-03 |
| HCN1 | 8uc8 | Voltage sensors in up configuration Closed pore | None | None | 484/660 | 3 | H. sapiens | Kim et al. | 2024-07-31 |
| HCN1 | 8uc7 | Voltage sensors in up configuration Closed pore | None | Propofol | 484/660 | 2.9 | H. sapiens | Kim et al. | 2024-07-31 |
| HCN1 | 8Y60 | Voltage sensors in up configuration Closed pore | None | Ivabradine Cholesterol | 473/890 | 3.23 | H. sapiens | Che et al. | 2025-10-29 |
| HCN1 | 9BC6 | Voltage sensors in up configuration Closed pore | M305L | Propofol | 484/660 | 2.5 | H. sapiens | Kim et al. | 2024-07-31 |
| HCN1 | 9BC7 | Voltage sensors in up configuration Closed pore | M305L | cAMP | 506/660 | 3.3 | H. sapiens | Kim et al. | 2024-07-31 |
| HCN3 | 8INZ | Voltage sensors in up configuration Closed pore | None | VX9a | 465/774 | 2.72 | H. sapiens | Yu et al. | 2024-04-10 |
| HCN3 | 8IO0 | Voltage sensors in up configuration Closed pore | None | cAMP | 473/774 | 3.19 | H. sapiens | Yu et al. | 2024-11-13 |
| HCN4 | 6GYN | Voltage sensors in up configuration Closed pore | None | None | 495/521 | 3.4 | H. sapiens | Shintre et al. | 2019-05-08 |
| HCN4 | 6GYO | Voltage sensors in up configuration Closed pore | None | cAMP | 501/521 | 3.4 | H. sapiens | Shintre et al. | 2019-05-01 |
| HCN4 | 7NMN | Voltage sensors disconnected from the pore Open pore | None | None | 469/889 | 3.6 | Oryctolagus cuniculus | Chaves-Sanjuan, A. | 2021-06-30 |
| HCN4 | 7NP3 | Voltage sensors in up configuration Open pore conductive | None | None | 490/892 | 3.3 | O. cuniculus | Giese et al. | 2021-08-11 |
| HCN4 | 7NP4 | Voltage sensors in up configuration Closed pore | None | cAMP | 501/892 | 3.3 | O. cuniculus | Giese et al. | 2021-08-11 |
| HCN4 | 8OFI | Voltage sensors in up configuration Open pore conductive | None | Ivabradine | 452/892 | 3.6 | O. cuniculus | Saponaro et al. | 2024-08-14 |
| Isoform . | PDB code . | State . | Muta-tions . | Ligand/Blocker/Modulator . | Modeled/total residues . | Resolu-tion (Å) . | Organism . | Deposition author/s . | Released . |
|---|---|---|---|---|---|---|---|---|---|
| HCN1 | 5U6O | Voltage sensors in up configuration Closed pore | None | None | 482/660 | 3.5 | H. sapiens | Lee et al. | 2017-01-25 |
| HCN1 | 5U6P | Voltage sensors in up configuration Closed pore | None | cAMP | 504/660 | 3.51 | H. sapiens | Lee et al. | 2017-01-25 |
| HCN1 | 6UQF | Voltage sensors in down configuration Closed pore | F186C S264C | cAMP | 531/660 | 3.04 | H. sapiens | Lee et al. | 2019-12-11 |
| HCN1 | 6UQG | Voltage sensors in up configuration Closed pore | Y289D | cAMP | 530/660 | 3.54 | H. sapiens | Lee et al. | 2019-12-11 |
| HCN1 | 8T4M | Voltage sensors in up configuration Closed pore | F186C S264C | cAMP | 533/890 | 3.16 | H. sapiens | Burtscher et al. | 2024-06-12 |
| HCN1 | 8T4Y | Voltage sensors Intermediate configuration Closed pore | F186C S264C C309A | cAMP | 501/890 | 3.58 | H. sapiens | Burtscher et al. | 2024-06-19 |
| HCN1 | 8T50 | Voltage sensors in down configuration Open pore conductive | F186C S264C | cAMP | 474/890 | 3.6 | H. sapiens | Burtscher et al. | 2024-07-03 |
| HCN1 | 8uc8 | Voltage sensors in up configuration Closed pore | None | None | 484/660 | 3 | H. sapiens | Kim et al. | 2024-07-31 |
| HCN1 | 8uc7 | Voltage sensors in up configuration Closed pore | None | Propofol | 484/660 | 2.9 | H. sapiens | Kim et al. | 2024-07-31 |
| HCN1 | 8Y60 | Voltage sensors in up configuration Closed pore | None | Ivabradine Cholesterol | 473/890 | 3.23 | H. sapiens | Che et al. | 2025-10-29 |
| HCN1 | 9BC6 | Voltage sensors in up configuration Closed pore | M305L | Propofol | 484/660 | 2.5 | H. sapiens | Kim et al. | 2024-07-31 |
| HCN1 | 9BC7 | Voltage sensors in up configuration Closed pore | M305L | cAMP | 506/660 | 3.3 | H. sapiens | Kim et al. | 2024-07-31 |
| HCN3 | 8INZ | Voltage sensors in up configuration Closed pore | None | VX9a | 465/774 | 2.72 | H. sapiens | Yu et al. | 2024-04-10 |
| HCN3 | 8IO0 | Voltage sensors in up configuration Closed pore | None | cAMP | 473/774 | 3.19 | H. sapiens | Yu et al. | 2024-11-13 |
| HCN4 | 6GYN | Voltage sensors in up configuration Closed pore | None | None | 495/521 | 3.4 | H. sapiens | Shintre et al. | 2019-05-08 |
| HCN4 | 6GYO | Voltage sensors in up configuration Closed pore | None | cAMP | 501/521 | 3.4 | H. sapiens | Shintre et al. | 2019-05-01 |
| HCN4 | 7NMN | Voltage sensors disconnected from the pore Open pore | None | None | 469/889 | 3.6 | Oryctolagus cuniculus | Chaves-Sanjuan, A. | 2021-06-30 |
| HCN4 | 7NP3 | Voltage sensors in up configuration Open pore conductive | None | None | 490/892 | 3.3 | O. cuniculus | Giese et al. | 2021-08-11 |
| HCN4 | 7NP4 | Voltage sensors in up configuration Closed pore | None | cAMP | 501/892 | 3.3 | O. cuniculus | Giese et al. | 2021-08-11 |
| HCN4 | 8OFI | Voltage sensors in up configuration Open pore conductive | None | Ivabradine | 452/892 | 3.6 | O. cuniculus | Saponaro et al. | 2024-08-14 |
All structures were obtained by single particle cryo-EM and comprise most of the channel proteins (see Modelled/total residues) with transmembrane (TMPC) and cytosolic part (CPC); in all cases, the flexible C and N termini remained unresolved. Structures were obtained without (apo) and with (holo) the natural ligand cAMP bound; in presence of the open-pore blocker (ivabradine) or potential modulators (propofol, cholesterol, and VX9). All proteins were isolated from non-polarized membranes (0 mV) and likewise solved without imposing voltage. In some cases (6UQF/6UQG; 8T50), prior to isolation, the S4 domain was fixed by metal cross-bridging in a down configuration mimicking the hyperpolarized-activated position. In most cases, the pore is in the closed state; for three cases (8T50; 7NP4; 8OFI), the pore is open and conductive (MD simulations).
VX9:4-[[(2S,4aR,6S,8aS)-6-[(4S,5R)-4-[(2S)-butan-2-yl]-5,9-dimethyl-decyl]-4a-methyl-2,3,4,5,6,7,8,8a-octahydro-1H-naphthalen-2-yl]oxy]-4-oxidanylidene-butanoic acid.