{"entity": "researcher", "timestamp": "2026-04-13T04:37:14.665Z", "family": "Frampton", "given": "Damon J A", "initials": "DJA", "orcid": "0000-0003-0941-3330", "affiliations": ["Department of Biomedical and Clinical Sciences, Link\u00f6ping University, Link\u00f6ping, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/53b76aac0cc44cada65e3f1cf3e32b8d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/53b76aac0cc44cada65e3f1cf3e32b8d"}}, "publications": [{"entity": "publication", "iuid": "9523ff0ce4c04bf7b05427729baa3b1d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9523ff0ce4c04bf7b05427729baa3b1d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9523ff0ce4c04bf7b05427729baa3b1d"}}, "title": "Subtype-specific modulation of human KV 7 channels by the anticonvulsant cannabidiol through a lipid-exposed pore-domain site.", "authors": [{"family": "P\u00f6kl", "given": "Michael", "initials": "M"}, {"family": "Sridhar", "given": "Akshay", "initials": "A"}, {"family": "Frampton", "given": "Damon J A", "initials": "DJA", "orcid": "0000-0003-0941-3330", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/53b76aac0cc44cada65e3f1cf3e32b8d.json"}}, {"family": "Linhart", "given": "Veronika A", "initials": "VA"}, {"family": "Delemotte", "given": "Lucie", "initials": "L", "orcid": "0000-0002-0828-3899", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87eaf619d7bd487ebdbe68c46b827e66.json"}}, {"family": "Liin", "given": "Sara I", "initials": "SI", "orcid": "0000-0001-8493-0114", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/236f04e5bac442599389f47248d54c75.json"}}], "type": "journal article", "published": "2023-12-00", "journal": {"title": "Br J Pharmacol", "issn": "1476-5381", "volume": "180", "issue": "23", "pages": "2956-2972", "issn-l": null}, "abstract": "Cannabidiol (CBD) is used clinically as an anticonvulsant. Its precise mechanism of action has remained unclear. CBD was recently demonstrated to enhance the activity of the neuronal KV 7.2/7.3 channel, which may be one important contributor to CBD anticonvulsant effect. Curiously, CBD inhibits the closely related cardiac KV 7.1/KCNE1 channel. Whether and how CBD affects other KV 7 subtypes remains uninvestigated and the CBD interaction sites mediating these diverse effects remain unknown.\n\nHere, we used electrophysiology, molecular dynamics simulations, molecular docking and site-directed mutagenesis to address these questions.\n\nWe found that CBD modulates the activity of all human KV 7 subtypes and that the effects are subtype dependent. CBD enhanced the activity of KV 7.2-7.5 subtypes, seen as a V50 shift towards more negative voltages or increased maximum conductance. In contrast, CBD inhibited the KV 7.1 and KV 7.1/KCNE1 channels, seen as a V50 shift towards more positive voltages and reduced conductance. In KV 7.2 and KV 7.4, we propose a CBD interaction site at the subunit interface in the pore domain that overlaps with the interaction site of other compounds, notably the anticonvulsant retigabine. However, CBD relies on other residues for its effects than the conserved tryptophan that is critical for retigabine effects. We propose a similar, though not identical CBD site in KV 7.1, with a non-conserved phenylalanine being important.\n\nWe identify novel targets of CBD, contributing to a better understanding of CBD clinical effects and provide mechanistic insights into how CBD modulates different KV 7 subtypes.", "doi": "10.1111/bph.16183", "pmid": "37377025", "labels": {"Lucie Delemotte": null, "SciLifeLab Fellow": null}, "xrefs": [], "notes": [], "created": "2024-11-26T05:25:44.868Z", "modified": "2025-04-11T07:23:23.673Z"}, {"entity": "publication", "iuid": "c570c42b458448aeb53cadd880bcd6fb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/c570c42b458448aeb53cadd880bcd6fb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/c570c42b458448aeb53cadd880bcd6fb"}}, "title": "Subtype-specific responses of hKv7.4 and hKv7.5 channels to polyunsaturated fatty acids reveal an unconventional modulatory site and mechanism.", "authors": [{"family": "Frampton", "given": "Damon J A", "initials": "DJA", "orcid": "0000-0003-0941-3330", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/53b76aac0cc44cada65e3f1cf3e32b8d.json"}}, {"family": "Choudhury", "given": "Koushik", "initials": "K", "orcid": "0000-0003-2350-3519", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5a8b2a41d0c4c82abd8bd57d9abff62.json"}}, {"family": "Nikesj\u00f6", "given": "Johan", "initials": "J", "orcid": "0000-0003-3852-1015", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/396f47856b034713840a18a22b6fca58.json"}}, {"family": "Delemotte", "given": "Lucie", "initials": "L", "orcid": "0000-0002-0828-3899", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87eaf619d7bd487ebdbe68c46b827e66.json"}}, {"family": "Liin", "given": "Sara I", "initials": "SI", "orcid": "0000-0001-8493-0114", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/236f04e5bac442599389f47248d54c75.json"}}], "type": "journal article", "published": "2022-06-01", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "11", "issn-l": "2050-084X"}, "abstract": "The KV7.4 and KV7.5 subtypes of voltage-gated potassium channels play a role in important physiological processes such as sound amplification in the cochlea and adjusting vascular smooth muscle tone. Therefore, the mechanisms that regulate KV7.4 and KV7.5 channel function are of interest. Here, we study the effect of polyunsaturated fatty acids (PUFAs) on human KV7.4 and KV7.5 channels expressed in Xenopus oocytes. We report that PUFAs facilitate activation of hKV7.5 by shifting the V50 of the conductance versus voltage (G(V)) curve toward more negative voltages. This response depends on the head group charge, as an uncharged PUFA analogue has no effect and a positively charged PUFA analogue induces positive V50 shifts. In contrast, PUFAs inhibit activation of hKV7.4 by shifting V50 toward more positive voltages. No effect on V50 of hKV7.4 is observed by an uncharged or a positively charged PUFA analogue. Thus, the hKV7.5 channel's response to PUFAs is analogous to the one previously observed in hKV7.1-7.3 channels, whereas the hKV7.4 channel response is opposite, revealing subtype-specific responses to PUFAs. We identify a unique inner PUFA interaction site in the voltage-sensing domain of hKV7.4 underlying the PUFA response, revealing an unconventional mechanism of modulation of hKV7.4 by PUFAs.", "doi": "10.7554/eLife.77672", "pmid": "35642964", "labels": {"SciLifeLab Fellow": null, "Lucie Delemotte": null}, "xrefs": [{"db": "pmc", "key": "PMC9159753"}, {"db": "pii", "key": "77672"}], "notes": [], "created": "2022-12-04T07:13:49.529Z", "modified": "2023-05-15T08:04:44.320Z"}]}