{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T08:18:34Z","timestamp":1791533914382,"version":"4.3.4"},"reference-count":151,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM109762"],"award-info":[{"award-number":["R01GM109762"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL131461"],"award-info":[{"award-number":["R01HL131461"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The delayed rectifier potassium IKs channel is an important regulator of the duration of the ventricular action potential. Hundreds of mutations in the genes (KCNQ1 and KCNE1) encoding the IKs channel cause long QT syndrome (LQTS). LQTS is a heart disorder that can lead to severe cardiac arrhythmias and sudden cardiac death. A better understanding of the IKs channel (here called the KCNQ1\/KCNE1 channel) properties and activities is of great importance to find the causes of LQTS and thus potentially treat LQTS. The KCNQ1\/KCNE1 channel belongs to the superfamily of voltage-gated potassium channels. The KCNQ1\/KCNE1 channel consists of both the pore-forming subunit KCNQ1 and the modulatory subunit KCNE1. KCNE1 regulates the function of the KCNQ1 channel in several ways. This review aims to describe the current structural and functional knowledge about the cardiac KCNQ1\/KCNE1 channel. In addition, we focus on the modulation of the KCNQ1\/KCNE1 channel and its potential as a target therapeutic of LQTS.<\/jats:p>","DOI":"10.3390\/ijms21249440","type":"journal-article","created":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T23:39:36Z","timestamp":1607902776000},"page":"9440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Insights into Cardiac IKs (KCNQ1\/KCNE1) Channels Regulation"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2098-7298","authenticated-orcid":false,"given":"Xiaoan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1688-2525","authenticated-orcid":false,"given":"H. Peter","family":"Larsson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"ref_1","first-page":"30","article-title":"Anatomy of the action potential in the heart","volume":"21","author":"Shih","year":"1994","journal-title":"Tex. Heart Inst. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1152\/advan.00105.2016","article-title":"Cardiac electrophysiology: Normal and ischemic ionic currents and the ECG","volume":"41","author":"Klabunde","year":"2017","journal-title":"Adv. Physiol. Educ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1152\/physrev.00002.2005","article-title":"Molecular physiology of cardiac repolarization","volume":"85","author":"Nerbonne","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_4","first-page":"127","article-title":"The long QT syndrome","volume":"2","author":"Vincent","year":"2002","journal-title":"Indian Pacing Electrophysiol. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1161\/CIRCEP.111.962019","article-title":"Long-QT syndrome: From genetics to management","volume":"5","author":"Schwartz","year":"2012","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3949\/ccjm.75.8.591","article-title":"Congenital long QT syndrome: Considerations for primary care physicians","volume":"75","author":"Levine","year":"2008","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e006558","DOI":"10.1161\/CIRCEP.118.006558","article-title":"Slow Delayed Rectifier Current Protects Ventricular Myocytes from Arrhythmic Dynamics Across Multiple Species: A Computational Study","volume":"11","author":"Varshneya","year":"2018","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Guo, X., Gao, X., Wang, Y., Peng, L., Zhu, Y., and Wang, S. (2012). IKs protects from ventricular arrhythmia during cardiac ischemia and reperfusion in rabbits by preserving the repolarization reserve. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031545"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1113\/jphysiol.1952.sp004764","article-title":"A quantitative description of membrane current and its application to conduction and excitation in nerve","volume":"117","author":"Hodgkin","year":"1952","journal-title":"J. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/384080a0","article-title":"Coassembly of KVLQT1 and minK (IsK) proteins to form cardiac IKs potassium channel","volume":"384","author":"Sanguinetti","year":"1996","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/384078a0","article-title":"KVLQT1 and lsK (minK) proteins associate to form the IKs cardiac potassium current","volume":"384","author":"Barhanin","year":"1996","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6093","DOI":"10.1113\/jphysiol.2011.220863","article-title":"Biophysical properties of slow potassium channels in human embryonic stem cell derived cardiomyocytes implicate subunit stoichiometry","volume":"589","author":"Wang","year":"2011","journal-title":"J. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1007\/s00246-012-0255-2","article-title":"Stoichiometry of the slow Iks potassium channel in human embryonic stem cell-derived myocytes","volume":"33","author":"Wang","year":"2012","journal-title":"Pediatr. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1113\/jphysiol.2014.287607","article-title":"The KCNQ1 channel\u2014Remarkable flexibility in gating allows for functional versatility","volume":"593","author":"Liin","year":"2015","journal-title":"J. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1126\/science.1116270","article-title":"Voltage sensor of Kv1.2: Structural basis of electromechanical coupling","volume":"309","author":"Long","year":"2005","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1085\/jgp.20028696","article-title":"Coupling between voltage sensors and activation gate in voltage-gated K+ channels","volume":"120","author":"Lu","year":"2002","journal-title":"J. Gen. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E6751","DOI":"10.1073\/pnas.1719105115","article-title":"S4-S5 linker movement during activation and inactivation in voltage-gated K+ channels","volume":"115","author":"Kalstrup","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5714","DOI":"10.1073\/pnas.1503488112","article-title":"Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel","volume":"112","author":"Liin","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e20272","DOI":"10.7554\/eLife.20272","article-title":"Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations","volume":"5","author":"Liin","year":"2016","journal-title":"Elife"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e51453","DOI":"10.7554\/eLife.51453","article-title":"Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms","volume":"9","author":"Bohannon","year":"2020","journal-title":"Elife"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0008-6363(98)00021-2","article-title":"Effects of the chromanol 293B, a selective blocker of the slow, component of the delayed rectifier K+ current, on repolarization in human and guinea pig ventricular myocytes","volume":"38","author":"Bosch","year":"1998","journal-title":"Cardiovasc. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1007\/s004240050240","article-title":"Inhibition of IKs in guinea pig cardiac myocytes and guinea pig IsK channels by the chromanol 293B","volume":"432","author":"Busch","year":"1996","journal-title":"Pfl\u00fcg. Arch."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1021\/jm970517u","article-title":"Class III antiarrhythmic activity in vivo by selective blockade of the slowly activating cardiac delayed rectifier potassium current IKs by (R)-2-(2,4-trifluoromethyl)-N-[2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]acetamide","volume":"40","author":"Selnick","year":"1997","journal-title":"J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"616","DOI":"10.3389\/fphar.2020.00616","article-title":"ArrhythmoGenoPharmacoTherapy","volume":"11","author":"Tosaki","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1161\/CIRCEP.108.789081","article-title":"Cardiac ion channels","volume":"2","author":"Grant","year":"2009","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jjcc.2018.10.011","article-title":"A trafficking-deficient KCNQ1 mutation, T587M, causes a severe phenotype of long QT syndrome by interfering with intracellular hERG transport","volume":"73","author":"Wu","year":"2019","journal-title":"J. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45911","DOI":"10.1038\/srep45911","article-title":"Gating mechanisms underlying deactivation slowing by two KCNQ1 atrial fibrillation mutations","volume":"7","author":"Peng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cardiores.2003.12.026","article-title":"Pharmacology of cardiac potassium channels","volume":"62","author":"Tamargo","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0163-7258(01)00116-4","article-title":"KCNQ potassium channels: Physiology, pathophysiology, and pharmacology","volume":"90","author":"Robbins","year":"2001","journal-title":"Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","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"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bpj.2015.11.023","article-title":"Voltage-Dependent Gating: Novel Insights from KCNQ1 Channels","volume":"110","author":"Cui","year":"2016","journal-title":"Biophys. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"237431","DOI":"10.1155\/2014\/237431","article-title":"Biology of the KCNQ1 potassium channel","volume":"2014","author":"Abbott","year":"2014","journal-title":"New J. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1469-7793.1998.037bz.x","article-title":"Voltage-dependent inactivation of the human K+ channel KvLQT1 is eliminated by association with minimal K+ channel (minK) subunits","volume":"510","author":"Sanguinetti","year":"1998","journal-title":"J. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1730","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":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","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":"ref_36","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.cell.2017.05.019","article-title":"Cryo-EM Structure of a KCNQ1\/CaM Complex Reveals Insights into Congenital Long QT Syndrome","volume":"169","author":"Sun","year":"2017","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nature07620","article-title":"Sensing voltage across lipid membranes","volume":"456","author":"Swartz","year":"2008","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e03606","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"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1085\/jgp.201210827","article-title":"Intermediate state trapping of a voltage sensor","volume":"140","author":"Lacroix","year":"2012","journal-title":"J. Gen. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6109","DOI":"10.1073\/pnas.1102724108","article-title":"Intermediate states of the Kv1.2 voltage sensor from atomistic molecular dynamics simulations","volume":"108","author":"Delemotte","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e53901","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":"ref_42","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.cell.2019.06.031","article-title":"Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel","volume":"178","author":"Wisedchaisri","year":"2019","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1085\/jgp.112.6.665","article-title":"Single-channel properties of IKs potassium channels","volume":"112","author":"Yang","year":"1998","journal-title":"J. Gen. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E996","DOI":"10.1073\/pnas.1214875110","article-title":"Single-channel basis for the slow activation of the repolarizing cardiac potassium current, IKs","volume":"110","author":"Werry","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"504","DOI":"10.3389\/fphys.2020.00504","article-title":"Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0006-3495(00)76586-6","article-title":"Gating and flickery block differentially affected by rubidium in homomeric KCNQ1 and heteromeric KCNQ1\/KCNE1 potassium channels","volume":"78","author":"Pusch","year":"2000","journal-title":"Biophys. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1113\/jphysiol.2003.046490","article-title":"Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels","volume":"552","author":"Seebohm","year":"2003","journal-title":"J. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/35003200","article-title":"A constitutively open potassium channel formed by KCNQ1 and KCNE3","volume":"403","author":"Schroeder","year":"2000","journal-title":"Nature"},{"key":"ref_49","first-page":"E7367","article-title":"KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions","volume":"114","author":"Ramentol","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"E1438","DOI":"10.1073\/pnas.1323548111","article-title":"Individual IKs channels at the surface of mammalian cells contain two KCNE1 accessory subunits","volume":"111","author":"Plant","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1586\/ecp.12.76","article-title":"KCNE genetics and pharmacogenomics in cardiac arrhythmias: Much ado about nothing?","volume":"6","author":"Abbott","year":"2013","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.neuron.2004.06.001","article-title":"KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity","volume":"42","author":"Melman","year":"2004","journal-title":"Neuron"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6439","DOI":"10.1074\/jbc.M010713200","article-title":"Structural determinants of KvLQT1 control by the KCNE family of proteins","volume":"276","author":"Melman","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1113\/jphysiol.2005.100644","article-title":"Interaction of KCNE subunits with the KCNQ1 K+ channel pore","volume":"570","author":"Panaghie","year":"2006","journal-title":"J. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1073\/pnas.0811897106","article-title":"Location of KCNE1 relative to KCNQ1 in the IKS potassium channel by disulfide cross-linking of substituted cysteines","volume":"106","author":"Chung","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1085\/jgp.200709805","article-title":"KCNE1 and KCNE3 stabilize and\/or slow voltage sensing S4 segment of KCNQ1 channel","volume":"130","author":"Nakajo","year":"2007","journal-title":"J. Gen. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1085\/jgp.200809976","article-title":"KCNQ1 and KCNE1 in the IKs channel complex make state-dependent contacts in their extracellular domains","volume":"131","author":"Xu","year":"2008","journal-title":"J. Gen. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.1113\/jphysiol.2008.157511","article-title":"Mechanisms by which atrial fibrillation-associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels","volume":"586","author":"Restier","year":"2008","journal-title":"J. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1085\/jgp.201110672","article-title":"Characterization of KCNQ1 atrial fibrillation mutations reveals distinct dependence on KCNE1","volume":"139","author":"Chan","year":"2012","journal-title":"J. Gen. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s12013-008-9032-5","article-title":"Structure, function, and modification of the voltage sensor in voltage-gated ion channels","volume":"52","author":"Borjesson","year":"2008","journal-title":"Cell Biochem. Biophys."},{"key":"ref_61","doi-asserted-by":"crossref","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":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.hrthm.2010.09.010","article-title":"R231C mutation in KCNQ1 causes long QT syndrome type 1 and familial atrial fibrillation","volume":"8","author":"Bartos","year":"2011","journal-title":"Heart Rhythm."},{"key":"ref_63","doi-asserted-by":"crossref","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":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"34212","DOI":"10.1074\/jbc.M112.364901","article-title":"KCNQ1 channels do not undergo concerted but sequential gating transitions in both the absence and the presence of KCNE1 protein","volume":"287","author":"Meisel","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7879","DOI":"10.1073\/pnas.1811623116","article-title":"IKs ion-channel pore conductance can result from individual voltage sensor movements","volume":"116","author":"Westhoff","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3750","DOI":"10.1038\/ncomms4750","article-title":"KCNE1 divides the voltage sensor movement in KCNQ1\/KCNE1 channels into two steps","volume":"5","author":"Rebolledo","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/417523a","article-title":"The open pore conformation of potassium channels","volume":"417","author":"Jiang","year":"2002","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1529\/biophysj.105.067165","article-title":"Differential roles of S6 domain hinges in the gating of KCNQ potassium channels","volume":"90","author":"Seebohm","year":"2006","journal-title":"Biophys. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/35002099","article-title":"Blocker protection in the pore of a voltage-gated K+ channel and its structural implications","volume":"403","author":"Holmgren","year":"2000","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nature20775","article-title":"Structural basis for gating the high-conductance Ca2+-activated K+ channel","volume":"541","author":"Hite","year":"2017","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1085\/jgp.20028569","article-title":"Scanning the intracellular S6 activation gate in the shaker K+ channel","volume":"119","author":"Hackos","year":"2002","journal-title":"J. Gen. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.1161\/01.RES.0000160555.58046.9a","article-title":"Autonomic control of cardiac action potentials: Role of potassium channel kinetics in response to sympathetic stimulation","volume":"96","author":"Terrenoire","year":"2005","journal-title":"Circ. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1161\/01.CIR.0000125523.14403.1E","article-title":"Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome","volume":"109","author":"Schwartz","year":"2004","journal-title":"Circulation"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1056\/NEJMoa022147","article-title":"Risk stratification in the long-QT syndrome","volume":"348","author":"Priori","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1113\/jphysiol.1990.sp017937","article-title":"Mechanism of receptor-mediated modulation of the delayed outward potassium current in guinea-pig ventricular myocytes","volume":"421","author":"Yazawa","year":"1990","journal-title":"J. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1161\/01.CIR.0000068344.54010.B3","article-title":"Probing the contribution of IKs to canine ventricular repolarization: Key role for beta-adrenergic receptor stimulation","volume":"107","author":"Volders","year":"2003","journal-title":"Circulation"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1126\/science.1066843","article-title":"Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel","volume":"295","author":"Marx","year":"2002","journal-title":"Science"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1161\/CIRCRESAHA.113.302982","article-title":"Exchange protein directly activated by cAMP mediates slow delayed-rectifier current remodeling by sustained beta-adrenergic activation in guinea pig hearts","volume":"114","author":"Aflaki","year":"2014","journal-title":"Circ. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"H880","DOI":"10.1152\/ajpheart.01138.2000","article-title":"Effects of sustained beta-adrenergic stimulation on ionic currents of cultured adult guinea pig cardiomyocytes","volume":"282","author":"Zhang","year":"2002","journal-title":"Am. J. Physiol. Heart. Circ. Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1146\/annurev.biophys.37.032807.125859","article-title":"PIP2 is a necessary cofactor for ion channel function: How and why?","volume":"37","author":"Suh","year":"2008","journal-title":"Annu. Rev. Biophys."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"530","DOI":"10.4161\/chan.25816","article-title":"The phosphoinositide sensitivity of the Kv channel family","volume":"7","author":"Kruse","year":"2013","journal-title":"Channels"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1113\/jphysiol.2007.132746","article-title":"On the physiological roles of PIP2 at cardiac Na+-Ca2+ exchangers and KATP channels: A long journey from membrane biophysics into cell biology","volume":"582","author":"Hilgemann","year":"2007","journal-title":"J. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5412","DOI":"10.1093\/emboj\/cdg526","article-title":"Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1\/KCNE1 voltage-gated potassium channels: A functional homology between voltage-gated and inward rectifier K+ channels","volume":"22","author":"Loussouarn","year":"2003","journal-title":"EMBO J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"9095","DOI":"10.1073\/pnas.1100872108","article-title":"KCNE1 enhances phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity of IKs to modulate channel activity","volume":"108","author":"Li","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"9825","DOI":"10.1523\/JNEUROSCI.2597-05.2005","article-title":"Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate","volume":"25","author":"Li","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1113\/jphysiol.2007.148254","article-title":"Kv7.1 (KCNQ1) properties and channelopathies","volume":"586","author":"Peroz","year":"2008","journal-title":"J. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","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":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","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":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"19411","DOI":"10.1074\/jbc.RA118.005401","article-title":"Phosphatidylinositol 4,5-bisphosphate (PIP2) regulates KCNQ3 K+ channels by interacting with four cytoplasmic channel domains","volume":"293","author":"Choveau","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/s42003-020-1104-0","article-title":"A PIP2 substitute mediates voltage sensor-pore coupling in KCNQ activation","volume":"3","author":"Liu","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/S0735-1097(02)02160-5","article-title":"Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with 31P-SLOOP magnetic resonance spectroscopy","volume":"40","author":"Beer","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"18922","DOI":"10.1073\/pnas.1315649110","article-title":"Intracellular ATP binding is required to activate the slowly activating K+ channel IKs","volume":"110","author":"Li","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11302-014-9436-1","article-title":"Cardiac purinergic signalling in health and disease","volume":"11","author":"Burnstock","year":"2015","journal-title":"Purinergic Signal."},{"key":"ref_94","first-page":"207","article-title":"Vascular and contractile responses to extracellular ATP: Studies in the isolated rat heart","volume":"1","author":"Hohl","year":"1985","journal-title":"Can. J. Cardiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/S100050010056","article-title":"Extracellular Adenosine Triphosphate Triggers Arrhythmias and Elemental Redistribution in Electrically Stimulated Rat Cardiac Myocytes","volume":"7","author":"Zhang","year":"2001","journal-title":"Microsc. Microanal."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/j.cellsig.2015.04.002","article-title":"Synergistic modulation of KCNQ1\/KCNE1 K+ channels (IKs) by phosphatidylinositol 4,5-bisphosphate (PIP2) and [ATP]i","volume":"27","author":"Kienitz","year":"2015","journal-title":"Cell. Signal."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"H757","DOI":"10.1152\/ajpheart.00246.2001","article-title":"Regulation of KATP channels by P2Y purinoceptors coupled to PIP2 metabolism in guinea pig ventricular cells","volume":"282","author":"Oketani","year":"2002","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.ccep.2016.01.005","article-title":"Adenosine Triphosphate-Sensitive Potassium Currents in Heart Disease and Cardioprotection","volume":"8","author":"Nichols","year":"2016","journal-title":"Card. Electrophysiol. Clin."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0735-1097(94)90438-3","article-title":"Adenosine triphosphate-sensitive potassium channel blocking agent ameliorates, but the opening agent aggravates, ischemia\/reperfusion-induced injury. Heart function studies in nonfibrillating isolated hearts","volume":"23","author":"Tosaki","year":"1994","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0735-1097(00)01183-9","article-title":"Mitochondrial ATP-sensitive K+ channels play a role in cardioprotection by Na+-H+ exchange inhibition against ischemia\/reperfusion injury","volume":"37","author":"Miura","year":"2001","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.pharmthera.2008.07.004","article-title":"The cardiac sarcolemmal ATP-sensitive potassium channel as a novel target for anti-arrhythmic therapy","volume":"120","author":"Billman","year":"2008","journal-title":"Pharmacol. Ther."},{"key":"ref_102","first-page":"750","article-title":"Positive regulation by chloride channel blockers of IsK channels expressed in Xenopus oocytes","volume":"46","author":"Busch","year":"1994","journal-title":"Mol. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1093\/emboj\/18.15.4137","article-title":"Stilbenes and fenamates rescue the loss of IKS channel function induced by an LQT5 mutation and other IsK mutants","volume":"18","author":"Abitbol","year":"1999","journal-title":"EMBO J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1124\/mol.119.117952","article-title":"The IKs Ion Channel Activator Mefenamic Acid Requires KCNE1 and Modulates Channel Gating in a Subunit-Dependent Manner","volume":"97","author":"Wang","year":"2020","journal-title":"Mol. Pharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e48576","DOI":"10.7554\/eLife.48576","article-title":"ML277 specifically enhances the fully activated open state of KCNQ1 by modulating VSD-pore coupling","volume":"8","author":"Hou","year":"2019","journal-title":"Elife"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5936","DOI":"10.1016\/j.bmcl.2012.07.060","article-title":"Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective Kv7.1 (KCNQ1) potassium channel activator","volume":"22","author":"Mattmann","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.bpj.2014.10.059","article-title":"Probing binding sites and mechanisms of action of an IKs activator by computations and experiments","volume":"108","author":"Xu","year":"2015","journal-title":"Biophys. J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"8732","DOI":"10.1073\/pnas.1300684110","article-title":"Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels","volume":"110","author":"Yu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Mruk, K., and Kobertz, W.R. (2009). Discovery of a novel activator of KCNQ1-KCNE1 K channel complexes. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004236"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nchembio874","article-title":"Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants","volume":"3","author":"Xiong","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"eaav0824","DOI":"10.1126\/sciadv.aav0824","article-title":"Deconstruction of an African folk medicine uncovers a novel molecular strategy for therapeutic potassium channel activation","volume":"4","author":"Manville","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1124\/mol.58.2.253","article-title":"Modulation of KCNQ2\/3 potassium channels by the novel anticonvulsant retigabine","volume":"58","author":"Main","year":"2000","journal-title":"Mol. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1523\/JNEUROSCI.21-15-05535.2001","article-title":"Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine","volume":"21","author":"Tatulian","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1038\/s41467-018-04266-w","article-title":"Direct neurotransmitter activation of voltage-gated potassium channels","volume":"9","author":"Manville","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"8116","DOI":"10.1038\/ncomms9116","article-title":"Atomic basis for therapeutic activation of neuronal potassium channels","volume":"6","author":"Kim","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e201912396","DOI":"10.1085\/jgp.201912396","article-title":"Polyunsaturated fatty acids produce a range of activators for heterogeneous IKs channel dysfunction","volume":"152","author":"Bohannon","year":"2020","journal-title":"J. Gen. Physiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jacc.2004.09.069","article-title":"Cellular and ionic mechanism for drug-induced long QT syndrome and effectiveness of verapamil","volume":"45","author":"Aiba","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e13471","DOI":"10.1111\/apha.13471","article-title":"Polyunsaturated fatty acid-derived IKs channel activators shorten the QT interval ex-vivo and in-vivo","volume":"229","author":"Skarsfeldt","year":"2020","journal-title":"Acta Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1002\/humu.21106","article-title":"The genetic basis of long QT and short QT syndromes: A mutation update","volume":"30","author":"Hedley","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1080\/07315724.2004.10719371","article-title":"Polyunsaturated fatty acids: Biochemical, nutritional and epigenetic properties","volume":"23","author":"Benatti","year":"2004","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"931","DOI":"10.17219\/acem\/31243","article-title":"PUFAs: Structures, Metabolism and Functions","volume":"24","author":"Berezinska","year":"2015","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1016\/j.celrep.2018.08.031","article-title":"Mechanisms Underlying the Dual Effect of Polyunsaturated Fatty Acid Analogs on Kv7.1","volume":"24","author":"Liin","year":"2018","journal-title":"Cell Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1529\/biophysj.108.130757","article-title":"Lipoelectric modification of ion channel voltage gating by polyunsaturated fatty acids","volume":"95","author":"Borjesson","year":"2008","journal-title":"Biophys. J."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e13186","DOI":"10.1111\/apha.13186","article-title":"\u03c9-6 and \u03c9-9 polyunsaturated fatty acids with double bonds near the carboxyl head have the highest affinity and largest effects on the cardiac IKs potassium channel","volume":"225","author":"Bohannon","year":"2019","journal-title":"Acta Physiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"11000","DOI":"10.1073\/pnas.92.24.11000","article-title":"Blocking effects of polyunsaturated fatty acids on Na+ channels of neonatal rat ventricular myocytes","volume":"92","author":"Xiao","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1073\/pnas.92.9.3997","article-title":"Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes","volume":"92","author":"Kang","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1073\/pnas.94.8.4182","article-title":"Suppression of voltage-gated L-type Ca2+ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes","volume":"94","author":"Xiao","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1016\/S0006-3495(00)76389-2","article-title":"MinK endows the IKs potassium channel pore with sensitivity to internal tetraethylammonium","volume":"79","author":"Sesti","year":"2000","journal-title":"Biophys. J."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/35416","article-title":"The conduction pore of a cardiac potassium channel","volume":"391","author":"Tai","year":"1998","journal-title":"Nature"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1085\/jgp.117.1.43","article-title":"TEA+-sensitive KCNQ1 constructs reveal pore-independent access to KCNE1 in assembled IKs channels","volume":"117","author":"Kurokawa","year":"2001","journal-title":"J. Gen. Physiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1124\/mol.106.031682","article-title":"Chromanol 293B binding in KCNQ1 (Kv7.1) channels involves electrostatic interactions with a potassium ion in the selectivity filter","volume":"71","author":"Lerche","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1124\/mol.64.1.70","article-title":"Molecular determinants of KCNQ1 channel block by a benzodiazepine","volume":"64","author":"Seebohm","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1097\/00005344-200301000-00018","article-title":"HMR 1556, a potent and selective blocker of slowly activating delayed rectifier potassium current","volume":"41","author":"Thomas","year":"2003","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1007\/s002100000284","article-title":"Inhibition of IKs channels by HMR 1556","volume":"362","author":"Gogelein","year":"2000","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"15922","DOI":"10.1038\/s41598-017-16218-3","article-title":"\u03b2-adrenergic stimulation augments transmural dispersion of repolarization via modulation of delayed rectifier currents IKs and IKr in the human ventricle","volume":"7","author":"Kang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"884","DOI":"10.3389\/fphys.2017.00884","article-title":"Evaluation of Optogenetic Electrophysiology Tools in Human Stem Cell-Derived Cardiomyocytes","volume":"8","author":"Bjork","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1124\/mol.110.066100","article-title":"The specific slow afterhyperpolarization inhibitor UCL2077 is a subtype-selective blocker of the epilepsy associated KCNQ channels","volume":"78","author":"Soh","year":"2010","journal-title":"Mol. Pharmacol."},{"key":"ref_138","first-page":"1218","article-title":"Molecular basis for differential sensitivity of KCNQ and I(Ks) channels to the cognitive enhancer XE991","volume":"57","author":"Wang","year":"2000","journal-title":"Mol. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.bcp.2018.03.016","article-title":"Molecular determinants of Kv7.1\/KCNE1 channel inhibition by amitriptyline","volume":"152","author":"Gazgalis","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ejphar.2018.02.013","article-title":"A novel role of the antitumor agent tricyclodecan-9-yl-xanthogenate as an open channel blocker of KCNQ1\/KCNE1","volume":"824","author":"Wu","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s00424-013-1352-7","article-title":"Insulin suppresses IKs (KCNQ1\/KCNE1) currents, which require \u03b2-subunit KCNE1","volume":"466","author":"Wu","year":"2014","journal-title":"Pfl\u00fcg. Arch."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1126\/science.280.5360.69","article-title":"The structure of the potassium channel: Molecular basis of K+ conduction and selectivity","volume":"280","author":"Doyle","year":"1998","journal-title":"Science"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1126\/science.2218530","article-title":"Mutations affecting TEA blockade and ion permeation in voltage-activated K+ channels","volume":"250","author":"MacKinnon","year":"1990","journal-title":"Science"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/0896-6273(92)90276-J","article-title":"The aromatic binding site for tetraethylammonium ion on potassium channels","volume":"8","author":"Heginbotham","year":"1992","journal-title":"Neuron"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/sj.bjp.0703086","article-title":"Differential tetraethylammonium sensitivity of KCNQ1-4 potassium channels","volume":"129","author":"Hadley","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1542-474X.2005.00077.x","article-title":"Safety and efficacy of flecainide in subjects with Long QT-3 syndrome (DeltaKPQ mutation): A randomized, double-blind, placebo-controlled clinical trial","volume":"10","author":"Moss","year":"2005","journal-title":"Ann. Noninvasive Electrocardiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0002-9149(96)00403-3","article-title":"Use of implantable cardioverter-defibrillators in the congenital long QT syndrome","volume":"78","author":"Groh","year":"1996","journal-title":"Am. J. Cardiol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.bbrc.2009.01.051","article-title":"Congenital long QT syndrome caused by the F275S KCNQ1 mutation: Mechanism of impaired channel function","volume":"380","author":"Li","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1056\/NEJM197110142851607","article-title":"Unilateral cervicothoracic sympathetic ganglionectomy for the treatment of long QT interval syndrome","volume":"285","author":"Moss","year":"1971","journal-title":"N. Engl. J. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1111\/chd.12855","article-title":"Left cardiac sympathetic denervation in the management of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia: A meta-regression","volume":"14","author":"Sgro","year":"2019","journal-title":"Congenit. Heart Dis."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1161\/01.CIR.100.18.1917","article-title":"Antiarrhythmic efficacy of selective blockade of the cardiac slowly activating delayed rectifier current, IKs, in canine models of malignant ischemic ventricular arrhythmia","volume":"100","author":"Lynch","year":"1999","journal-title":"Circulation"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9440\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:43:51Z","timestamp":1760179431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,11]]},"references-count":151,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21249440"],"URL":"https:\/\/doi.org\/10.3390\/ijms21249440","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,11]]}}}