Targeting hyperpolarisation-activated cyclic nucleotide-gated channels in the treatment of neurological disorders

Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants
Cunningham, K. 2025. Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants. Ion Channel Modulation Symposium (ICMS) 2025. Cambridge, UK 25 - 26 Jun 2025

BPS2025 - Pufa stabilizes a conductive state of the selectivity filter in IKs channels
Golluscio, Alessia, Eldstrom, Jodene R., Jowais, Jessica J., Perez-Rodriguez, Marta E., Cunningham, Kevin P., Cruz, Alicia de la, Wu, Xiaoan, Corradi, Valentina, Tieleman, D. Peter, Fedida, David and Larsson, Peter H. 2025. BPS2025 - Pufa stabilizes a conductive state of the selectivity filter in IKs channels. Biophysical Journal. 124 (3, Supplement 1), p. 124a. https://doi.org/10.1016/j.bpj.2024.11.706

PUFA stabilizes a conductive state of the selectivity filter in IKs channels
Alessia Golluscio, Jodene Eldstrom, Jessica J. Jowais, Marta Elena Perez, Kevin Peter Cunningham, Alicia De La Cruz, Xiaoan Wu, Valentina Corradi, D. Peter Tieleman, David Fedida and H. Peter Larsson 2024. PUFA stabilizes a conductive state of the selectivity filter in IKs channels. eLife. 13 RP95852. https://doi.org/10.7554/elife.95852

Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants
Elizabeth D. Kim, Xiaoan Wu, Sangyun Lee, Gareth R. Tibbs, Kevin P. Cunningham, Eleonora Di Zanni, Marta E. Perez, Peter A. Goldstein, Alessio Accardi, H. Peter Larsson and Crina M. Nimigean 2024. Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants. Nature. 632, pp. 451-459. https://doi.org/10.1038/s41586-024-07743-z

Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism
Wu, X, Cunningham, K.P., Bruening-Wright, A, Pandey, S and Larsson, H. P. 2024. Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism. International Journal of Molecular Sciences. 25 (8) 4309. https://doi.org/10.3390/ijms25084309

Preprint: Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism
Xiaoan Wu, Kevin P. Cunningham, Andrew Bruening-Wright, Shilpi Pandey and H. Peter Larsson 2024. Preprint: Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism. Preprints.org. https://doi.org/10.20944/preprints202403.0499.v1

Preprint: Binding of PUFA stabilizes a conductive state of the selectivity filter in IKs channels
Alessia Golluscio, Jodene Eldstrom, Jessica J. Jowais, Marta E. Perez-Rodriguez, Kevin P. Cunningham, Alicia de la Cruz, Xiaoan Wu, David Fedida and H. Peter Larsson 2024. Preprint: Binding of PUFA stabilizes a conductive state of the selectivity filter in IKs channels. arXiv. https://doi.org/10.1101/2024.01.11.575247

Similar voltage-sensor movement in spHCN channels can cause closing, opening, or inactivation
Xiaoan Wu, Kevin P. Cunningham, Rosamary Ramentol, Marta E. Perez and H. Peter Larsson 2023. Similar voltage-sensor movement in spHCN channels can cause closing, opening, or inactivation. Journal of General Physiology. 155 (5) e202213170. https://doi.org/10.1085/jgp.202213170

Artemisinin inhibits neutrophil and macrophage chemotaxis, cytokine production and NET release
Morad, H.O.J., Luqman, S., Garcia Pinto, L., Cunningham, K., Vilar, B., Clayton, G., Shankar-Hari, M. and McNaughton, P.A. 2022. Artemisinin inhibits neutrophil and macrophage chemotaxis, cytokine production and NET release. Scientific Reports. 2022 (12) 11078. https://doi.org/10.1038/s41598-022-15214-6

Preprint: Artemisinin inhibits innate immune cell chemotaxis, cytokine production and NET release
Morad, H., Luqman, S., Pinto, L., Cunningham, K.P., Vilar, B., Clayton, G., Shankar-Hari, M. and McNaughton, P.A. 2022. Preprint: Artemisinin inhibits innate immune cell chemotaxis, cytokine production and NET release. https://doi.org/10.21203/rs.3.rs-1335980/v1

The Prostacyclin Analogue, Treprostinil, Used in the Treatment of Pulmonary Arterial Hypertension, is a Potent Antagonist of TREK-1 and TREK-2 Potassium Channels
Cunningham, K., Clapp. L.H., Mathie, A. and Veale, E.L. 2021. The Prostacyclin Analogue, Treprostinil, Used in the Treatment of Pulmonary Arterial Hypertension, is a Potent Antagonist of TREK-1 and TREK-2 Potassium Channels. Frontiers in Pharmacology. 12 705421. https://doi.org/10.3389/fphar.2021.705421

Two-Pore Domain Potassium Channels as Drug Targets: Anesthesia and Beyond.
Mathie, A., Veale, E.L., Cunningham, K.P., Holden, R.G. and Wright, P.D. 2021. Two-Pore Domain Potassium Channels as Drug Targets: Anesthesia and Beyond. Annual Review of Pharmacology and Toxicology. 61, pp. 401-420. https://doi.org/10.1146/annurev-pharmtox-030920-111536

Effects of the ventilatory stimulant, doxapram on human TASK‐3 (KCNK9, K2P9.1) channels and TASK‐1 (KCNK3, K2P3.1) channels
Kevin P. Cunningham, D. Euan MacIntyre, Alistair Mathie and Emma L. Veale 2020. Effects of the ventilatory stimulant, doxapram on human TASK‐3 (KCNK9, K2P9.1) channels and TASK‐1 (KCNK3, K2P3.1) channels. Acta Physiologica. 228 (2) e13361. https://doi.org/10.1111/apha.13361

Characterization and regulation of wild‐type and mutant TASK‐1 two pore domain potassium channels indicated in pulmonary arterial hypertension
Cunningham, K.P., Holden, R.G., Escribano‐Subias, P.M., Cogolludo, A., Veale, E.L. and Mathie, A. 2019. Characterization and regulation of wild‐type and mutant TASK‐1 two pore domain potassium channels indicated in pulmonary arterial hypertension. Journal of Physiology. 597 (4), pp. 1087-1101. https://doi.org/10.1113/jp277275