{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:34:25Z","timestamp":1791340465359,"version":"4.3.1"},"reference-count":66,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS110847"],"award-info":[{"award-number":["R01NS110847"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,5,31]]},"abstract":"<jats:p>Neuronal KCNQ channels mediate the M-current, a key regulator of membrane excitability in the central and peripheral nervous systems. Mutations in KCNQ2 channels cause severe neurodevelopmental disorders, including epileptic encephalopathies. However, the impact that different mutations have on channel function remains poorly defined, largely because of our limited understanding of the voltage-sensing mechanisms that trigger channel gating. Here, we define the parameters of voltage sensor movements in wt-KCNQ2 and channels bearing epilepsy-associated mutations using cysteine accessibility and voltage clamp fluorometry (VCF). Cysteine modification reveals that a stretch of eight to nine amino acids in the S4 becomes exposed upon voltage sensing domain activation of KCNQ2 channels. VCF shows that the voltage dependence and the time course of S4 movement and channel opening\/closing closely correlate. VCF reveals different mechanisms by which different epilepsy-associated mutations affect KCNQ2 channel voltage-dependent gating. This study provides insight into KCNQ2 channel function, which will aid in uncovering the mechanisms underlying channelopathies.<\/jats:p>","DOI":"10.7554\/elife.77030","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T08:01:25Z","timestamp":1654070485000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.77030","source":"Crossref","is-referenced-by-count":17,"title":["Distinctive mechanisms of epilepsy-causing mutants discovered by measuring S4 movement in KCNQ2 channels"],"prefix":"10.7554","volume":"11","author":[{"given":"Michaela A","family":"Edmond","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02dgjyy92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Miller School of Medicine, University of Miami","place":["Miami, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Hinojo-Perez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02dgjyy92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Miller School of Medicine, University of Miami","place":["Miami, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2098-7298","authenticated-orcid":true,"given":"Xiaoan","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05nbqxr67","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology and Biophysics, Miller School of Medicine, University of Miami","place":["Miami, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta E","family":"Perez Rodriguez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05nbqxr67","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology and Biophysics, Miller School of Medicine, University of Miami","place":["Miami, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4804-2739","authenticated-orcid":true,"given":"Rene","family":"Barro-Soria","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02dgjyy92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Miller School of Medicine, University of Miami","place":["Miami, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1096\/fj.14-0501ufm","article-title":"Ion channels under the sun","volume":"28","author":"Abbott","year":"2014","journal-title":"FASEB Journal"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1113\/jphysiol.1982.sp014411","article-title":"Pharmacological inhibition of the M-current","volume":"332","author":"Adams","year":"1982","journal-title":"The Journal of Physiology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1242\/jeb.124.1.259","article-title":"Slow synaptic transmission in frog sympathetic ganglia","volume":"124","author":"Adams","year":"1986","journal-title":"The Journal of Experimental Biology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/s0896-6273(00)80143-9","article-title":"Contribution of the S4 segment to gating charge in the Shaker K+ channel","volume":"16","author":"Aggarwal","year":"1996","journal-title":"Neuron"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1085\/jgp.201812221","article-title":"Epilepsy-associated mutations in the voltage sensor of KCNQ3 affect voltage dependence of channel opening","volume":"151","author":"Barro-Soria","year":"2019","journal-title":"The Journal of General Physiology"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1212\/WNL.0b013e3181fd6170","article-title":"Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy","volume":"75","author":"Brodie","year":"2010","journal-title":"Neurology"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/283673a0","article-title":"Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone","volume":"283","author":"Brown","year":"1980","journal-title":"Nature"},{"key":"bib8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-02-j0003.2002","article-title":"Benign familial neonatal convulsions caused by altered gating of KCNQ2\/KCNQ3 potassium channels","volume":"22","author":"Castaldo","year":"2002","journal-title":"The Journal of Neuroscience"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.siny.2018.01.004","article-title":"Neonatal epilepsies: Clinical management","volume":"23","author":"Cornet","year":"2018","journal-title":"Seminars in Fetal & Neonatal Medicine"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/s0896-6273(01)00487-1","article-title":"Tight steric closure at the intracellular activation gate of a voltage-gated K(+) channel","volume":"32","author":"del Camino","year":"2001","journal-title":"Neuron"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/nrn1785","article-title":"Pathways modulating neural KCNQ\/M (Kv7) potassium channels","volume":"6","author":"Delmas","year":"2005","journal-title":"Nature Reviews. Neuroscience"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1038\/nn.4589","article-title":"Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains","volume":"20","author":"Geisheker","year":"2017","journal-title":"Nature Neuroscience"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1085\/jgp.201411221","article-title":"Capturing distinct KCNQ2 channel resting states by metal ion bridges in the voltage-sensor domain","volume":"144","author":"Gourgy-Hacohen","year":"2014","journal-title":"The Journal of General Physiology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s00018-016-2359-y","article-title":"Modulation of Kv7 channels and excitability in the brain","volume":"74","author":"Greene","year":"2017","journal-title":"Cellular and Molecular Life Sciences"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/0006-8993(82)90954-4","article-title":"Voltage-clamp analysis of muscarinic excitation in hippocampal neurons","volume":"250","author":"Halliwell","year":"1982","journal-title":"Brain Research"},{"key":"bib16","volume-title":"Ion Channels of Excitable Membranes","author":"Hille","year":"2001"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0092-8240(05)80004-7","article-title":"A quantitative description of membrane current and its application to conduction and excitation in nerve","volume":"52","author":"Hodgkin","year":"1990","journal-title":"Bulletin of Mathematical Biology"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1085\/jgp.114.2.277","article-title":"Allosteric voltage gating of potassium channels I. Mslo ionic currents in the absence of Ca(2+)","volume":"114","author":"Horrigan","year":"1999","journal-title":"The Journal of General Physiology"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01911-8","article-title":"Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening","volume":"8","author":"Hou","year":"2017","journal-title":"Nature Communications"},{"key":"bib20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14406-w","article-title":"Two-stage electro-mechanical coupling of a KV channel in voltage-dependent activation","volume":"11","author":"Hou","year":"2020","journal-title":"Nature Communications"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/35036198","article-title":"Neuronal KCNQ potassium channels: physiology and role in disease","volume":"1","author":"Jentsch","year":"2000","journal-title":"Nature Reviews. Neuroscience"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1152\/physiol.00031.2005","article-title":"The KCNQ1 potassium channel: from gene to physiological function","volume":"20","author":"Jespersen","year":"2005","journal-title":"Physiology (Bethesda, Md.)"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1111\/epi.12200","article-title":"Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation","volume":"54","author":"Kato","year":"2013","journal-title":"Epilepsia"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"E9702","DOI":"10.1073\/pnas.1705802114","article-title":"PIP2 mediates functional coupling and pharmacology of neuronal KCNQ channels","volume":"114","author":"Kim","year":"2017","journal-title":"PNAS"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/s0092-8674(00)80556-5","article-title":"KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness","volume":"96","author":"Kubisch","year":"1999","journal-title":"Cell"},{"key":"bib26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0220415","article-title":"Upgraded molecular models of the human KCNQ1 potassium channel","volume":"14","author":"Kuenze","year":"2019","journal-title":"PLOS ONE"},{"key":"bib27","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-46312-4","volume-title":"Principles of Fluorescence Spectroscopy","author":"Lakowicz","year":"2006"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/s0896-6273(00)80056-2","article-title":"Transmembrane movement of the shaker K+ channel S4","volume":"16","author":"Larsson","year":"1996","journal-title":"Neuron"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.molcel.2020.10.037","article-title":"Structural Basis for the Modulation of Human KCNQ4 by Small-Molecule Drugs","volume":"81","author":"Li","year":"2021","journal-title":"Molecular Cell"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/s41422-020-00410-8","article-title":"Molecular basis for ligand activation of the human KCNQ2 channel","volume":"31","author":"Li","year":"2021","journal-title":"Cell Research"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1126\/science.1116269","article-title":"Crystal structure of a mammalian voltage-dependent Shaker family K+ channel","volume":"309","author":"Long","year":"2005","journal-title":"Science (New York, N.Y.)"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/B978-0-444-63326-2.00002-8","article-title":"Potassium channel genes and benign familial neonatal epilepsy","volume":"213","author":"Maljevic","year":"2014","journal-title":"Progress in Brain Research"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1126\/science.271.5246.213","article-title":"Direct physical measure of conformational rearrangement underlying potassium channel gating","volume":"271","author":"Mannuzzu","year":"1996","journal-title":"Science (New York, N.Y.)"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1529\/biophysj.107.128371","article-title":"Gating consequences of charge neutralization of arginine residues in the S4 segment of K(v)7.2, an epilepsy-linked K+ channel subunit","volume":"95","author":"Miceli","year":"2008","journal-title":"Biophysical Journal"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1016\/j.bpj.2012.02.004","article-title":"Gating currents from Kv7 channels carrying neuronal hyperexcitability mutations in the voltage-sensing domain","volume":"102","author":"Miceli","year":"2012","journal-title":"Biophysical Journal"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"e10","DOI":"10.1111\/epi.13601","article-title":"Infantile spasms and encephalopathy without preceding neonatal seizures caused by KCNQ2 R198Q, a gain-of-function variant","volume":"58","author":"Millichap","year":"2017","journal-title":"Epilepsia"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1152\/physrev.00002.2005","article-title":"Molecular physiology of cardiac repolarization","volume":"85","author":"Nerbonne","year":"2005","journal-title":"Physiological Reviews"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1002\/ana.24080","article-title":"Dominant-negative effects of KCNQ2 mutations are associated with epileptic encephalopathy","volume":"75","author":"Orhan","year":"2014","journal-title":"Annals of Neurology"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"22710","DOI":"10.1073\/pnas.1016300108","article-title":"KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate","volume":"107","author":"Osteen","year":"2010","journal-title":"PNAS"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"18751","DOI":"10.1073\/pnas.1014150107","article-title":"The cardiac IKs channel, complex indeed","volume":"107","author":"Osteen","year":"2010","journal-title":"PNAS"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"7103","DOI":"10.1073\/pnas.1201582109","article-title":"Allosteric gating mechanism underlies the flexible gating of KCNQ1 potassium channels","volume":"109","author":"Osteen","year":"2012","journal-title":"PNAS"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.neulet.2009.08.071","article-title":"The KCNQ2\/3 selective channel opener ICA-27243 binds to a novel voltage-sensor domain site","volume":"465","author":"Padilla","year":"2009","journal-title":"Neuroscience Letters"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1085\/jgp.200409197","article-title":"The cooperative voltage sensor motion that gates a potassium channel","volume":"125","author":"Pathak","year":"2005","journal-title":"The Journal of General Physiology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1016\/S0140-6736(12)61480-9","article-title":"Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study","volume":"380","author":"Rauch","year":"2012","journal-title":"Lancet (London, England)"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1124\/jpet.108.137794","article-title":"In vivo profile of ICA-27243 [N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide], a potent and selective KCNQ2\/Q3 (Kv7.2\/Kv7.3) activator in rodent anticonvulsant models","volume":"326","author":"Roeloffs","year":"2008","journal-title":"The Journal of Pharmacology and Experimental Therapeutics"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/ana.23620","article-title":"Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome","volume":"72","author":"Saitsu","year":"2012","journal-title":"Annals of Neurology"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"12619","DOI":"10.1073\/pnas.0601176103","article-title":"Voltage-dependent conformational changes in human Ca(2+)- and voltage-activated K(+) channel, revealed by voltage-clamp fluorometry","volume":"103","author":"Savalli","year":"2006","journal-title":"PNAS"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"24089","DOI":"10.1074\/jbc.M003245200","article-title":"KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents","volume":"275","author":"Schroeder","year":"2000","journal-title":"The Journal of Biological Chemistry"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1016\/s0896-6273(00)80142-7","article-title":"Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel","volume":"16","author":"Seoh","year":"1996","journal-title":"Neuron"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"5311","DOI":"10.1523\/JNEUROSCI.3919-13.2014","article-title":"Conditional deletions of epilepsy-associated KCNQ2 and KCNQ3 channels from cerebral cortex cause differential effects on neuronal excitability","volume":"34","author":"Soh","year":"2014","journal-title":"The Journal of Neuroscience"},{"key":"bib51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2117640119","article-title":"KCNQ2 and KCNQ5 form heteromeric channels independent of KCNQ3","volume":"119","author":"Soh","year":"2022","journal-title":"PNAS"},{"key":"bib52","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20143382","article-title":"Epileptic Encephalopathy In A Patient With A Novel Variant In The Kv7.2 S2 Transmembrane Segment: Clinical, Genetic, and Functional Features","volume":"20","author":"Soldovieri","year":"2019","journal-title":"International Journal of Molecular Sciences"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.cell.2019.12.003","article-title":"Structural Basis of Human KCNQ1 Modulation and Gating","volume":"180","author":"Sun","year":"2020","journal-title":"Cell"},{"key":"bib54","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.53901","article-title":"Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state","volume":"9","author":"Taylor","year":"2020","journal-title":"eLife"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1085\/jgp.200809978","article-title":"Voltage clamp fluorimetry reveals a novel outer pore instability in a mammalian voltage-gated potassium channel","volume":"132","author":"Vaid","year":"2008","journal-title":"The Journal of General Physiology"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/ng0196-17","article-title":"Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias","volume":"12","author":"Wang","year":"1996","journal-title":"Nature Genetics"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1126\/science.282.5395.1890","article-title":"KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel","volume":"282","author":"Wang","year":"1998","journal-title":"Science (New York, N.Y.)"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1002\/ana.22644","article-title":"KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy","volume":"71","author":"Weckhuysen","year":"2012","journal-title":"Annals of Neurology"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1212\/01.wnl.0000435296.72400.a1","article-title":"Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients","volume":"81","author":"Weckhuysen","year":"2013","journal-title":"Neurology"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1124\/mol.107.043216","article-title":"N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide (ICA-27243): a novel, selective KCNQ2\/Q3 potassium channel activator","volume":"73","author":"Wickenden","year":"2008","journal-title":"Molecular Pharmacology"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1038\/nrd2983","article-title":"Voltage-gated potassium channels as therapeutic targets","volume":"8","author":"Wulff","year":"2009","journal-title":"Nature Reviews. Drug Discovery"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1124\/mol.104.010793","article-title":"The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate","volume":"67","author":"Wuttke","year":"2005","journal-title":"Molecular Pharmacology"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1517\/13543784.15.10.1167","article-title":"Novel anticonvulsant drugs targeting voltage-dependent ion channels","volume":"15","author":"Wuttke","year":"2006","journal-title":"Expert Opinion on Investigational Drugs"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1085\/jgp.103.2.321","article-title":"Shaker potassium channel gating. III: Evaluation of kinetic models for activation","volume":"103","author":"Zagotta","year":"1994","journal-title":"The Journal of General Physiology"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"13180","DOI":"10.1073\/pnas.1305167110","article-title":"Kv7.1 ion channels require a lipid to couple voltage sensing to pore opening","volume":"110","author":"Zaydman","year":"2013","journal-title":"PNAS"},{"key":"bib66","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03606","article-title":"Domain-domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel","volume":"3","author":"Zaydman","year":"2014","journal-title":"eLife"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/77030\/elife-77030-v3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/77030\/elife-77030-v3.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/77030","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:16:35Z","timestamp":1697058995000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/77030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,1]]},"references-count":66,"alternative-id":["10.7554\/eLife.77030"],"URL":"https:\/\/doi.org\/10.7554\/elife.77030","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.01.19.476944","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2022.01.19.476944","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.77030.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.77030.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.77030.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,1]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e77030"}}