Erlandsdotter LM , Giammarino L , Halili A , Nikesjö J , Gréen H , Odening KE , Liin SI .

             ion channel activity
             cardiac muscle cell action potential

	Fig. 1. 17$𝛽$ -E2 inhibits the Kv7.1/KCNE1 channel. (A) Molecular structure of the steroid backbone and indicated steroid sex hormones. (B) Summary of the effect of indicated concentrations of steroid sex hormones on Gmax of Kv7.1/KCNE1. TMC, time-matched control (perfusion with control solution); E1, estrone; 17β-E2: estradiol; E3, estriol; Prog, progesterone; Test, testosterone. Data are shown as means ± SEM. n = 4 to 18 (table S1). Statistics indicate a one-sample t test compared to a hypothetical value of 0 (i.e., no change in Gmax). ****P < 0.0001. P > 0.05 [not significant (n.s.)] for all other data (table S1). (C) Representative current family with corresponding G(V) curve of Kv7.1/KCNE1 in the absence (left) and presence (middle) of 10 μM 17β-E2. Used voltage protocol is shown as inset. Curves in the G(V) plot (right) represent Boltzmann fits (see Materials and Methods for details). For this specific cell, V50,ctrl = +31 mV, Itailmax,ctrl = 4.2 μA, V50,17β-E2 = +28 mV, and Itailmax,17β-E2 = 1.2 μA. (D) Same as in (C) but for progesterone. For this specific cell, V50,ctrl = +25 mV, Itailmax,ctrl = 3.4 μA, V50,Prog = +28 mV, and Itailmax,Prog = 3.8 μA. (E) Time course of onset/washout of 17β-E2 effect assessed by stepping to +40 mV from a holding voltage of −80 mV every 30 s (quantified at the end of the +40-mV pulse). Dashed line, current amplitude before 17β-E2 application. (F) Concentration dependence of the 17β-E2 effect on Gmax of Kv7.1/KCNE1. See Materials and Methods for details of the concentration-response fit. Best fit, maximum ∆Gmax = −94% and IC50 = 5.2 μM. Data are shown as means ± SEM. n = 4 to 18. Small error bars are covered by symbols. (G) Same as in (F) but for current amplitude at +40 mV. Best fit, maximum ∆I40 mV = −95% and IC50 = 5.3 μM.
	Fig. 2. 17$𝛽$ -E2 inhibition of Kv7.1/KCNE1 is KCNE1 dependent. (A) Representative current family with corresponding G(V) curve of Kv7.1 in the absence (left) and presence (middle) of 10 μM 17β-E2. Curves in the G(V) plot (right) represent Boltzmann fits. For this specific cell, V50,ctrl = −23 mV, Itailmax,ctrl = 2.1 μA, V50,17β-E2 = −24 mV, and Itailmax,17β-E2 = 2.0 μA. (B) Same as in (A) but for Kv7.1_F351A and 10 μM 17β-E2. For this specific cell, V50,ctrl = +34 mV, Itailmax,ctrl = 1.9 μA, V50,17β-E2 = +34 mV, and Itailmax,17β-E2 = 2.3 μA. (C) Amino acid sequence of KCNE1. Numbers indicate sites for truncations. Gray bar indicates the transmembrane portion of KCNE1. (D) Summary of the effect of 3 and 10 μM 17β-E2 on Kv7.1/KCNE1 channels with indicated KCNE1 truncations. Data are shown as means ± SEM. n = 4 to 13 (defined in table S2). Statistics indicate one-way analysis of variance (ANOVA) followed by Dunnett’s multiple comparisons test to determine whether the 17β-E2 effect on truncated channels deviates from the effect on WT. **P < 0.01, ***P < 0.001, and ****P < 0.0001. P > 0.05 (n.s.) for all other data (see table S2). Gray and black dashed lines indicate the effect of 3 and 10 μM 17β-E2, respectively, on WT Kv7.1/KCNE1.
	Fig. 3. 17$𝛽$ -E2 inhibition of Kv7.1/KCNE1 is PKC dependent. (A) Left: An overview of used receptor or kinase inhibitors with indicated primary target. Right: A summary of the effect of either control solution only (open bars, “−17β-E2”) or 10 μM 17β-E2 (closed bars, “+17β-E2”) on Kv7.1/KCNE1 exposed to indicated inhibitors (see Materials and Methods for details). The dashed bar for PKCε inhibitory peptide (IP) denotes data for oocytes injected with PKCε IP. Data are shown as means ± SEM. n = 3 to 9 (defined in table S3). Statistics indicate one-way ANOVA followed by Dunnett’s multiple comparisons test to determine whether the 17β-E2 effect in the presence of inhibitors deviates from the effect on WT (included as bar marked “Ctrl”). *P < 0.05, **P < 0.01, and ****P < 0.0001. P > 0.05 (n.s.) for all other data (see table S3). (B) Representative current family with corresponding G(V) curve of chelerythrine-treated Kv7.1/KCNE1 in the absence (left) and presence (middle) of 10 μM 17β-E2. Curves in the G(V) plot (right) represent Boltzmann fits. For this specific cell, V50,ctrl = +20 mV, Itailmax,ctrl = 1.0 μA, V50,17β-E2 = +15 mV, and Itailmax,17β-E2 = 1.1 μA.
	Fig. 4. 17$𝛽$ -E2 inhibition of Kv7.1/KCNE1 is dependent on KCNE1/S68A but not dynamin. (A) Representative current family with corresponding G(V) curve of dynasore-treated Kv7.1/KCNE1 in the absence (left) and presence (middle) of 10 μM 17β-E2. Curves in the G(V) plot (right) represent Boltzmann fits. For this specific cell, V50,ctrl = +40 mV, Itailmax,ctrl = 2.2 μA, V50,17β-E2 = +39 mV, and Itailmax,17β-E2 = 0.4 μA. (B) Representative current family with corresponding G(V) curve of Kv7.1/KCNE1_S68A in the absence (left) and presence (middle) of 10 μM 17β-E2. Curves in the G(V) plot (right) represent Boltzmann fits. For this specific cell, V50,ctrl = +49 mV, Itailmax,ctrl = 0.6 μA, V50,17β-E2 = +50 mV, and Itailmax,17β-E2 = 0.6 μA. (C) Same as in (B) but for Kv7.1/KCNE1_S68D. For this specific cell, V50,ctrl = +42 mV, Itailmax,ctrl = 1.2 μA, V50,17β-E2 = +45 mV, and Itailmax,17β-E2 = 0.4 μA. (D) Summary of the effect of 10 μM 17β-E2 on Kv7.1/KCNE1 channels with indicated inhibitor or KCNE1 mutations. Data are shown as means ± SEM. n = 3 to 18. Statistics indicate one-way ANOVA followed by Dunnett’s multiple comparisons test to determine whether the 17β-E2 effect deviates from the effect on WT (included as bar marked “Ctrl”). ***P < 0.001. P > 0.05 (n.s.) for all other data (see also table S3). Open bar (“-17β-E2”) denotes Kv7.1/KCNE1 exposed to the indicated inhibitor in the absence of 17β-E2 (see Materials and Methods for details). The black dashed line indicates the effect of 10 μM 17β-E2 on WT Kv7.1/KCNE1.
	Fig. 5. LQTS-associated mutations in KCNE1 alter the 17$𝛽$ -E2 effect. (A) Summary of the effect of 3 and 10 μM 17β-E2 on Kv7.1/KCNE1 channels with indicated LQTS-associated mutations in KCNE1. Data are shown as means ± SEM. n = 3 to 10 (defined in table S4). Statistics indicate one-way ANOVA followed by Dunnett’s multiple comparisons test to determine whether the 17β-E2 effect on mutated channels deviates from the effect on WT. *P < 0.05, **P < 0.01, and ****P < 0.0001. P > 0.05 (n.s.) for all other data (see table S4). Gray and black dashed lines indicate the effect of 3 and 10 μM 17β-E2, respectively, on WT Kv7.1/KCNE1. (B) Representative current family with corresponding G(V) curve of Kv7.1/KCNE1_S74L in the absence (left) and presence (middle) of 10 μM 17β-E2. Curves in the G(V) plot (right) represent Boltzmann fits. For this specific cell, V50,ctrl = +44 mV, Itailmax,ctrl = 3.1 μA, V50,17β-E2 = +47 mV, and Itailmax,17β-E2 = 1.4 μA. (C) Same as in (B) but for Kv7.1/KCNE1_K70N. For this specific cell, V50,ctrl = +57 mV, Itailmax,ctrl = 6.2 μA, V50,17β-E2 = +61 mV, and Itailmax,17β-E2 = 5.1 μA. (D) Same as in (B) but for Kv7.1/KCNE1_H73Y. For this specific cell, V50,ctrl = +61 mV, Itailmax,ctrl = 2.9 μA, V50,17β-E2 = +68 mV, and Itailmax,17β-E2 = 3.5 μA.
	Fig. 6. Determining the combined burden of LQTS-associated mutation and 17$𝛽$ -E2 effect. (A) The relative steady-state current amplitude at +40 mV of indicated Kv7.1/KCNE1 LQTS-associated mutants under control conditions (0 μM) and in the presence of 3 and 10 μM 17β-E2 (“3 μM” and “10 μM,” respectively), normalized to the current amplitude of WT Kv7.1/KCNE1 under control conditions. The combined burden of a mutation and 17β-E2 was determined by multiplying the control amplitude for each mutant [0 μM in (A)] with the mean 17β-E2–induced decrease in steady-state current amplitude at +40 mV (reported in fig. S8). See Materials and Methods for details. Data are shown as means ± SEM. n = 3 to 10. ND denotes not determined because of unquantifiable current amplitudes of the S68T mutant at +40 mV. (B) Schematic illustration of KCNE1 highlighting LQTS-associated mutations in KCNE1 with preserved WT-like response to 17β-E2 (left) and mutations with reduced (S68T and K70N) or abolished (R67C and H73Y) response to 17β-E2. (C) Bottom view of Kv7.1/KCNE1 highlighting proposed interactions between the C terminus of KCNE1 and the lower part S1 (e.g., W120), S5 (e.g., R259, Q260, and I263), and S6 (e.g., K362 and H363) of Kv7.1. Figure inspired by (46) and made using their model of Kv7.1/KCNE1 in the activated open state (PDBDEV: 00000042). Note that H73 is in an unresolved region and not included in the model.
	Fig. 7. 17$𝛽$ -E2 effect on tail current of IKs in ventricular cardiomyocytes isolated from female rabbits. (A) Representative current traces in the absence (black) or presence (gray) of 30 μM chromanol 293B in a control cell (Cm = 128 pF) and in a cell incubated with 0.06% (v/v) DMSO (Cm = 132 pF) or 3 μM 17β-E2 (Cm = 248 pF) or 3 nM 17β-E2 (Cm = 147 pF). (B) IKs tail current-voltage (I-V) relationships, using the voltage protocol indicated in Materials and Methods. IKs was obtained as chromanol 293B (30 μM)–sensitive current. Values are shown in the figure as means ± SEM. Statistical analysis was performed using two-way ANOVA followed by Bonferroni post hoc analysis. (C) Effect of 17β-E2 on IKs tail at +40 mV. Data are shown as means ± SEM. Statistical analysis was performed using one-way ANOVA followed by Bonferroni post hoc analysis. (D to F) Summary of the effect of 17β-E2 with DMSO as stock solvent on indicated constructs expressed in Xenopus oocytes. (D) Concentration dependence of the 17β-E2 effect on current amplitude at +40 mV of Kv7.1/KCNE1 upon dissolving 17β-E2 in DMSO. The curve represents concentration-response fit. Best fit, maximum ∆I40 mV = −77% and EC50 = 185 nM. Data are shown as means ± SEM. n = 3 to 8. The corresponding data for 17β-E2 dissolved in EtOH (from Fig. 1G) is included for comparison. (E) Lack of effect of 17β-E2 dissolved in DMSO on Kv7.1 alone, in line with experiments using 17β-E2 dissolved in EtOH (shown in fig. S1A). Data are shown as means ± SEM. n = 5. (F) Preserved WT-like response of the S74L mutation and abolished response of the H73Y mutation to 17β-E2 dissolved in DMSO, in line with experiments using 17β-E2 dissolved in EtOH (shown in Figs. 5 and 6). Data are shown as means ± SEM. n = 3 to 5.
	Figure S1. 17β-E2 effect on Kv7.1 or concatenated Kv7.1/KCNE1 channels. A) Concentration dependence of the 17β-E2 effect on Gmax (left) and V50 (right) of Kv7.1 alone. B) Same as in A but for concatenated Kv7.1/KCNE1 channels promoting indicated stoichiometries. Data are shown as mean ± sem. n = 4-18. Best fit for E1-Kv7.1: maximum ∆Gmax = -90%, EC50 = 6.6 µM. Best fit for E1-Kv7.1- Kv7.1: maximum ∆Gmax = -89%, EC50 = 15.2 µM. Data for co-injected Kv7.1/KCNE1 is included for comparison (dashed line or filled black symbols). Note that the experimental data for E1-Kv7.1 and E1-Kv7.1-Kv7.1 is deviating from the concentration-response fit, in particular at the lowest concentration, indicating a Hill coefficient greater than 1. However, because of the uncertainty in the concentration-response fit with unconstrained Hill coefficient (a 95% confidence interval of 0.6-2.4), the Hill coefficient was constrained to 1 (as described in the Materials and Methods) and the meaning of a potentially steeper concentration-response relationship should be interpreted with caution. C) Statistical comparison of the effect of 3 and 10 µM 17β-E2 on indicated constructs. Statistics indicate one-way ANOVA followed by Dunnett’s multiple comparison test, to determine if Gmax of concatenated constructs deviates from that of co-injected Kv7.1/KCNE1. * denotes P < 0.05. P > 0.05 (n.s.) for all other data. Data are shown as mean ± sem. n = as in panel B.
	Figure S2. Part of the KCNE1 C terminus is required for 17β-E2-mediated inhibition of Kv7.1/KCNE1. A) Representative current family with corresponding G(V) curve of Kv7.1/KCNE1_2-38 in the absence (left) and presence (middle) of 10 µM 17β-E2. Curves in the G(V) plot (right) represent Boltzmann fits. For this specific cell: V50,ctrl = +54 mV, Itailmax,ctrl = 3.9 µA, V50,17β-E2 = +63 mV, Itailmax,17β-E2 = 3.0 µA. B) Same as in A but for Kv7.1/KCNE1_67. For this specific cell: V50,ctrl = +11 mV, Itailmax,ctrl = 2.4 µA, V50,17β-E2 = +12 mV, Itailmax,17β-E2 = 2.6 µA. C) Same as in A but for Kv7.1/KCNE1_78. For this specific cell: V50,ctrl = +63 mV, Itailmax,ctrl = 1.0 µA, V50,17β-E2 = +66 mV, Itailmax,17β-E2 = 0.5 µA. D) Same as in A but for Kv7.1/KCNE1_80. For this specific cell: V50,ctrl = +74 mV, Itailmax,ctrl = 3.3 µA, V50,17β-E2 = +72 mV, Itailmax,17β-E2 = 0.7 µA. E) Same as in A but for Kv7.1/KCNE1_102. For this specific cell: V50,ctrl = +44 mV, Itailmax,ctrl = 4.5 µA, V50,17β-E2 = +45 mV, Itailmax,17β-E2 = 1.3 µA.
	Figure S3. Effect of the PKC activator PMA on Gmax of the Kv7.1/KCNE1 channel. Summary of the effect of 1 nM of PMA on Gmax of wild-type Kv7.1/KCNE1 under control conditions or in the presence of the PKC inhibitor chelerythrine. Data are shown as mean ± sem. n = 6-9. Statistics for PMA alone indicates one-sample t-test compared to a hypothetical value of 0 (i.e. no change in Gmax); # denotes P < 0.05. Statistics for the comparison of the PMA effect with chelerythrine to that without chelerythrine indicates Student’s t-test; ** denotes P < 0.01.
	Figure S4. Impact of how a heterozygous setting affects the 17β-E2 response of LQTS-associated mutations with deviating 17β-E2 response. Summary of the effect of 3 and 10 µM 17β-E2 on Kv7.1/KCNE1 channels with indicated LQTS-associated mutations in KCNE1. “Het.” denotes a heterozygous setting, in which WT Kv7.1 was co-injected with mutant KCNE1 and WT KCNE1 in a 1:1 molar ratio. Data are shown as mean ± sem. n = 4-6. “Hom.” denotes a homozygous setting, in which WT Kv7.1 was co-injected with mutant KCNE1 (the same data as shown in Figure 5). WT data is included for comparison. Grey and black dashed lines indicate the effect of 3 and 10 µM 17β-E2, respectively, on wild-type Kv7.1/KCNE1.
	Figure S5. V50 of Kv7.1/KCNE1 channels with LQTS-associated mutations and 17β-E2 effect on V50. An overview of V50 under control conditions (denoted by “0 µM 17β-E2”) for wild-type Kv7.1/KCNE1 and Kv7.1/KCNE1 channels with indicated LQTS-associated mutations. Data are shown as mean ± sem. n = 4-34 (defined in Table S5). Dashed line denotes V50 for wild-type. “3 µM 17β-E2” and “10 µM 17β-E2” denotes V50 of indicated LQTS-associated mutations in the presence of these concentrations of 17β-E2. Data are shown as mean ± sem. n = 3-10 (defined in Table S4).
	Figure S6. 17β-E2 effect on steady-state current amplitude at +40 mV of Kv7.1/KCNE1 channels with LQTS-associated mutations. The effect of 3 and 10 µM 17β-E2 on steady-state current amplitude at +40 mV (quantified at the end of the 5 s-long test pulse) on Kv7.1/KCNE1 channels with indicated LQTS-associated mutations. Data are shown as mean ± sem. n = 3-10 (defined in Table S4). Current amplitude has been normalized to the current amplitude of wild-type Kv7.1/KCNE1 under control conditions (indicated by dashed line). ND denotes not determined because of the unquantifiable current amplitude of the S68T mutant at +40 mV.

Ackerman, Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. 2003, Pubmed

Ackerman, Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome. 2003, Pubmed
Alzamora, Sexual dimorphism and oestrogen regulation of KCNE3 expression modulates the functional properties of KCNQ1 K⁺ channels. 2011, Pubmed
Ando, Synergic effects of β-estradiol and erythromycin on hERG currents. 2011, Pubmed
Aranda, Nuclear hormone receptors and gene expression. 2001, Pubmed
Barhanin, K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. 1996, Pubmed , Xenbase
Berger, Effects of 17beta-estradiol on action potentials and ionic currents in male rat ventricular myocytes. 1997, Pubmed
Bjelic, Sex hormones and repolarization dynamics during the menstrual cycle in women with congenital long QT syndrome. 2022, Pubmed
Braun, PKCβII specifically regulates KCNQ1/KCNE1 channel membrane localization. 2020, Pubmed
Chen, Physical and functional interaction sites in cytoplasmic domains of KCNQ1 and KCNE1 channel subunits. 2020, Pubmed
Davies, Specificity and mechanism of action of some commonly used protein kinase inhibitors. 2000, Pubmed
Doolen, Conventional protein kinase C isoforms regulate human dopamine transporter activity in Xenopus oocytes. 2002, Pubmed , Xenbase
Drici, Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. 1996, Pubmed
Druzin, Mechanism of estradiol-induced block of voltage-gated K+ currents in rat medial preoptic neurons. 2011, Pubmed
Edwards, Regulation of signal transduction pathways by estrogen and progesterone. 2005, Pubmed
Efendiev, PKC-beta and PKC-zeta mediate opposing effects on proximal tubule Na+,K+-ATPase activity. 1999, Pubmed
El-Sherif, Acquired Long QT Syndrome and Electrophysiology of Torsade de Pointes. 2019, Pubmed
Fuentes, Estrogen receptor signaling mechanisms. 2019, Pubmed
Galleano, Functional cross-talk between phosphorylation and disease-causing mutations in the cardiac sodium channel Nav1.5. 2021, Pubmed , Xenbase
Gou, Specific protein kinase C isoform exerts chronic inhibition on the slowly activating delayed-rectifier potassium current by affecting channel trafficking. 2021, Pubmed
Granados, The molecular nature of the 17β-Estradiol binding site in the voltage- and Ca2+-activated K+ (BK) channel β1 subunit. 2019, Pubmed
Guettler, The impact of age on long QT syndrome. 2019, Pubmed
Han, Regulation of aquaporin-4 water channels by phorbol ester-dependent protein phosphorylation. 1998, Pubmed
Hassan, Regulation of anion exchanger Slc26a6 by protein kinase C. 2007, Pubmed , Xenbase
Hedley, The genetic basis of long QT and short QT syndromes: a mutation update. 2009, Pubmed
Hou, Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening. 2017, Pubmed , Xenbase
Kang, Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel. 2008, Pubmed
Kang, Calmodulin acts as a state-dependent switch to control a cardiac potassium channel opening. 2020, Pubmed
Kathöfer, Human beta(3)-adrenoreceptors couple to KvLQT1/MinK potassium channels in Xenopus oocytes via protein kinase C phosphorylation of the KvLQT1 protein. 2003, Pubmed , Xenbase
Kauthale, Assessment of temperature-induced hERG channel blockade variation by drugs. 2015, Pubmed
Kim, Development of a Patient-Specific p.D85N-Potassium Voltage-Gated Channel Subfamily E Member 1-Induced Pluripotent Stem Cell-Derived Cardiomyocyte Model for Drug-Induced Long QT Syndrome. 2021, Pubmed
Kow, Rapid estrogen actions on ion channels: A survey in search for mechanisms. 2016, Pubmed
Kroncke, Structural basis for KCNE3 modulation of potassium recycling in epithelia. 2016, Pubmed
Kuenze, Allosteric mechanism for KCNE1 modulation of KCNQ1 potassium channel activation. 2020, Pubmed
Kurokawa, Acute effects of oestrogen on the guinea pig and human IKr channels and drug-induced prolongation of cardiac repolarization. 2008, Pubmed
Lai, Cooperation of Genomic and Rapid Nongenomic Actions of Estrogens in Synaptic Plasticity. 2017, Pubmed
Lai, Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms. 2005, Pubmed
Larsson, KCNE1 tunes the sensitivity of KV7.1 to polyunsaturated fatty acids by moving turret residues close to the binding site. 2018, Pubmed , Xenbase
Li, KCNE1 enhances phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity of IKs to modulate channel activity. 2011, Pubmed , Xenbase
Liin, Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel. 2015, Pubmed , Xenbase
Liin, Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations. 2016, Pubmed , Xenbase
Lopes, Protein kinase A modulates PLC-dependent regulation and PIP2-sensitivity of K+ channels. 2007, Pubmed , Xenbase
Lvov, Identification of a protein-protein interaction between KCNE1 and the activation gate machinery of KCNQ1. 2010, Pubmed
Lösel, Nongenomic actions of steroid hormones. 2003, Pubmed
Möller, Effects of estradiol on cardiac ion channel currents. 2006, Pubmed
Na, 17β-Estradiol attenuates the activity of the glutamate transporter type 3 expressed in Xenopus oocytes. 2012, Pubmed , Xenbase
Nerbonne, Molecular physiology of cardiac repolarization. 2005, Pubmed
Nerbonne, Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium. 2000, Pubmed
Norman, Steroid-hormone rapid actions, membrane receptors and a conformational ensemble model. 2004, Pubmed
O'Hara, Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation. 2011, Pubmed
Odening, How do sex hormones modify arrhythmogenesis in long QT syndrome? Sex hormone effects on arrhythmogenic substrate and triggered activity. 2014, Pubmed
Odening, Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility. 2019, Pubmed
Peyton, Involvement of epidermal growth factor receptor signaling in estrogen inhibition of oocyte maturation mediated through the G protein-coupled estrogen receptor (Gper) in zebrafish (Danio rerio). 2011, Pubmed
Piacentino, Cellular basis of abnormal calcium transients of failing human ventricular myocytes. 2003, Pubmed
Ponte, Mechanisms of drug induced QT interval prolongation. 2010, Pubmed
Pougnet, ATP P2X receptors downregulate AMPA receptor trafficking and postsynaptic efficacy in hippocampal neurons. 2014, Pubmed
Rapetti-Mauss, Oestrogen promotes KCNQ1 potassium channel endocytosis and postendocytic trafficking in colonic epithelium. 2013, Pubmed
Rocheleau, Secondary structure of a KCNE cytoplasmic domain. 2006, Pubmed , Xenbase
Roden, Clinical practice. Long-QT syndrome. 2008, Pubmed
Rodriguez, Drug-induced QT prolongation in women during the menstrual cycle. 2001, Pubmed
Sanguinetti, Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. 1996, Pubmed , Xenbase
Sauer, Long QT syndrome in adults. 2007, Pubmed
Scholz, Central role of PKCα in isoenzyme-selective regulation of cardiac transient outward current Ito and Kv4.3 channels. 2011, Pubmed , Xenbase
Schwartz, Prevalence of the congenital long-QT syndrome. 2009, Pubmed
Splawski, Mutations in the hminK gene cause long QT syndrome and suppress IKs function. 1997, Pubmed , Xenbase
Tanabe, Effects of estrogen on action potential and membrane currents in guinea pig ventricular myocytes. 1999, Pubmed
Thomas, The structural biology of oestrogen metabolism. 2013, Pubmed
Vijayaragavan, Modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by protein kinase A and protein kinase C. 2004, Pubmed , Xenbase
Waldegger, Inhibition of minK protein induced K+ channels in Xenopus oocytes by estrogens. 1996, Pubmed , Xenbase
Wang, Stoichiometry of the slow I(ks) potassium channel in human embryonic stem cell-derived myocytes. 2012, Pubmed
Wang, Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes. 2020, Pubmed
Wolbrette, Risk of proarrhythmia with class III antiarrhythmic agents: sex-based differences and other issues. 2003, Pubmed
Wu, Insights into Cardiac IKs (KCNQ1/KCNE1) Channels Regulation. 2020, Pubmed
Xiao, Evidence for functional role of epsilonPKC isozyme in the regulation of cardiac Na(+) channels. 2001, Pubmed , Xenbase
Yang, A multiscale computational modelling approach predicts mechanisms of female sex risk in the setting of arousal-induced arrhythmias. 2017, Pubmed
Yu, Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels. 2013, Pubmed
Zaltsman, Rapid desensitization of the TRH receptor and persistent desensitization of its constitutively active mutant. 2000, Pubmed , Xenbase
Zhang, Cannabidiol activates neuronal Kv7 channels. 2022, Pubmed