Zaydman MA , Kasimova MA , McFarland K , Beller Z , Hou P , Kinser HE , Liang H , Zhang G , Shi J , Tarek M , Cui J .

R01 HL070393 NHLBI NIH HHS , R01 NS060706 NINDS NIH HHS , R01-HL70393 NHLBI NIH HHS , R01-NS060706 NINDS NIH HHS , T32 HL007873 NHLBI NIH HHS

	Figure 1. KCNE1 suppresses the intermediate-open state of KCNQ1.(A–H) Fluorescence (green) and current (black) signals from Xenopus oocytes injected with cRNA encoding pseudo-WT (C214A/G219C/C331A) KCNQ1 alone (KCNQ1, A–D) or coinjected with cRNAs encoding pseudo-WT KCNQ1 and KCNE1 (KCNQ1+KCNE1, E–H). The cells were labeled with Alexa 488 C5-maleimide. (A and E) GV and FV relationships (solid) with the main and high voltage FV components plotted (dotted lines). (B and F) normalized fluorescence and current responses to a 60 mV pulse shown with fits (thin grey lines) to a single- or bi-exponential function. Averaged fast (C and G) and slow (D and H) tau values of fluorescence and current responses to various voltage pulses. (I) Intermediate- (E1-R2, top) and activated- (E1-R4, bottom) state homology models of KCNQ1 after 100 ns of MD simulation. Side view of one VSD (left) and bottom view of the pore (right). (J) Currents from the cells expressing E160R/R231E (E1R/R2E, top) or E160R/R237E (E1R/R4E, bottom) both alone (−KCNE1, middle) or with KCNE1 (+KCNE1, right).DOI: http://dx.doi.org/10.7554/eLife.03606.003Figure 1—figure supplement 1. Improved resolution of Fhigh.(A and B) VCF data from cells expressing pseudo-WT KCNQ1, labeled with Alexa 546 C5-maleimide (KCNQ1 [Alexa 546]). (C and D) VCF data from pseudo-WT KCNQ1+R67E/K69E/K70E KCNE1 labeled with Alexa 488 C5-maleimide (KCNQ1+RKK/EEE [Alexa488]). (A and C) Normalized current and fluorescence responses to a 60 mV pulse. (B and D) GV and FV relationships (solid) with the main and high voltage FV components plotted (dotted lines). Current signals (black), fluorescence signals (color, red = Alexa 546, green = Alexa 488). The RKK/EEE mutation in KCNE1 causes a leftward shift of Fmain, relative to that of WT KCNE1, which increases the separation between Fmain and Fhigh.DOI: http://dx.doi.org/10.7554/eLife.03606.004
	Figure 1—figure supplement 2. GV/FV relationships are maintained in channels the mutation R243Q in KCNQ1.GV (solid black) and FV (solid green) relationships for R243Q/psWT KCNQ1 channels expressed alone (R243Q) (A) or with R67E/K69E/K70E KCNE1 (R243Q+RKK/EEE) (B). Green dotted lines show the main and high voltage FV components. The GV relationship of pseudo-WT channels (black dashed lines) is significantly different from that of R243Q; however, the relationship of the GV to different FV components are preserved.DOI: http://dx.doi.org/10.7554/eLife.03606.005
	Figure 1—figure supplement 3. MD simulations predict that, unlike the resting-state, both the intermediate- and activated-states of the VSD stabilize pore opening through state-dependent protein and lipid interactions.(A) Snapshots of one VSD (left, side view) or the pore domain (right, bottom view) following 100 ns of MD simulations. In the resting, intermediate or activated VSD, E160 (E1, red) forms a salt bridge with R228 (R1), R231 (R2) or R237 (R4), respectively. (B) Averaged (over several trajectories) pore radius vs position along the axis normal to the membrane (Z). (C) Snapshots of the PIP2 intrasubunit-binding site in the three states. In the resting/closed state, PIP2 interacts with positive residues of S4 (cyan). When the VSD is intermediate or activated, PIP2 shifts closer to S6 (yellow) and anchors its positive residues (K354 and K358). (D) Probability of salt bridges formation between positive residues of S6 (K354 and K358) and PIP2. The lipid interacts with S6 only when the VSD is intermediate or activated, not when it is resting. Error bars represent SD. K354 and K358 interactions are not statistically different for the E1-R2 and E1-R4 states. Figure 1—figure supplement 3B represents the averaged pore radius profiles along the axis normal to the membrane (Z). In the activated/open and intermediate states, the minimal radiuses of the pore at this level are 3.5 ± 0.4 Å and 2.8 ± 0.6 Å respectively. For comparison, in the Kv1.2 open state, the corresponding radius (pdb 3LUT [Chen et al., 2010]) is 4.2 Å, in the Kv1.2/2.1 paddle chimera open state (pdb 2 R9R [Long et al., 2007]) it is 4.2 Å also, and in the NavMS open state (pdb 3ZJZ [Loussouarn et al., 2003]) it is 2.3 Å. Therefore, the minimal pore radius at the intercellular gate level in the models of the Kv7.1 activated and intermediate states corresponds to the open pore. In the resting/closed state, this radius decreases to 1.5 ± 0.5 Å. This is similar to the closed states of KcsA (pdb 1K4C [Zhou et al., 2001]), NavAB (pdb 4EKW [Payandeh et al., 2012]) and NavAP (pdb 4DXW [Zhang et al., 2012]), where these values are 1.1, 1.2 and 0.9 Å respectively. The activated/open, intermediate and resting/closed states of Kv7.1 differ by their properties as evidenced from the reported experimental data. Taking advantage of our simulations, we attempted to investigate whether the interactions between PIP2 and positive residues of the Kv7.1 intrasubunit binding site are different. Indeed PIP2 interacts preferably with the VSD (S4) when the channel is resting/closed or with the pore (S6) when the channel is activated/open (Kasimova et al., 2014) (Figure 1—figure supplement 3C, top and bottom panels). In the intermediate state, the lipid forms salt bridges with both S4 (R243) and S6 (K354 and K358) simultaneously (Figure 1—figure supplement 3C, middle panel). Its equilibrium position is also between these in the activated/open and resting/closed states. Interestingly, the probability of interaction between PIP2 and S6 (K354 and K358) is rather high (Figure 1—figure supplement 3D). The average values are slightly higher for the intermediate than for the activated/open states: 40 and 26% for K354, 68 and 42% for K358 respectively. However, this difference is statistically insignificant due to the estimated error bars.DOI: http://dx.doi.org/10.7554/eLife.03606.006
	Figure 1—figure supplement 4. VSD mutations reveal that KCNE1 suppresses currents from intermediate-open states and increases those from activated-open states.(A) Cartoons illustrating the mutational strategy used to arrest the VSD near the intermediate- and activated-states. The E160R (E1R) mutation was used to disrupt the native electrostatic interactions between the S2 and S4 segments that stabilize the VSD as it undergoes activation. E1R was paired with R231E (R2E) or R237E (R4E) to stabilize the putative intermediate- and activated-states, respectively. (B) Currents from oocytes expressing WT or mutant KCNQ1 subunits alone (−KCNE1, left) or with KCNE1 (+KCNE1, right) in response various voltage test pulses. (C and D) Averaged steady-state current–voltage relationships for cells expressing WT or mutant KCNQ1 subunits alone (C, −KCNE1) or with KCNE1 (D, +KCNE1).DOI: http://dx.doi.org/10.7554/eLife.03606.007
	Figure 1—figure supplement 5. Surface membrane expression of E1R/R2E and E1R/R4E.Biotinylation of intact oocytes allowed separation of membrane proteins from the cell lysate using streptavidin beads. The membrane fraction and the cell lysate were subjected to Western Blot using antibodies against KCNQ1 (Top) or Gβ, a soluble protein not found in the membrane. (A) E1R/R2E and E1R/R4E reached the cell membrane with similar efficiency. (B) KCNE1 did not decrease the expression of E1R/R2E to the membrane.DOI: http://dx.doi.org/10.7554/eLife.03606.008
	Figure 2. Permeation and pharmacological properties depend on VSD conformation.Currents from cells expressing WT KCNQ1 alone (KCNQ1, black), E160R/R231E (E1R/R2E, red), E160R/R237E alone (E1R/R4E, blue), E160R/R237E+KCNE1 (E1R/R4E+KCNE1, green), or WT KCNQ1+KCNE1 (KCNQ1+KCNE1, grey). (A) Currents from a single cell in external solutions containing 100 mM of Na+, K+, or Rb+. The currents were elicited by first stepping the voltage to +60 mV for 5 s then to −60 mV for 3 s tails. (B) Averaged Rb+/K+ permeability ratios calculated by comparing the tail current amplitudes. (C). Currents before (CTL) and after (XE991) bath application of 5 μM XE991 in the external solution. (D) Fraction of original current inhibited after 2 s of depolarization vs concentration of XE991 applied shown with fits to the hill equation with a hill coefficient of 1. N.S. = not significant.DOI: http://dx.doi.org/10.7554/eLife.03606.009Figure 2—figure supplement 1. Inhibition of KCNQ1+KCNE1 channels by XE991 develops slowly over time.Currents in response to a +60 mV test pulse from oocytes expressing KCNQ1 (A) or KCNQ1+KCNE1 (B), recorded in control (CTL) and 5 μM XE991 external solutions. (C) Time dependence of XE991 inhibition—the averaged ratio of the current in 5 μM XE991 to that in control solutions is plotted vs depolarization time. (D) Averaged fraction inhibited after 200 (dashed line), 500 (thin line) or 2000 (thick line) ms of depolarization is plotted vs concentration of XE991 for oocytes expressing WT KCNQ1 (black) or WT KCNQ1+KCNE1 (grey).DOI: http://dx.doi.org/10.7554/eLife.03606.010
	Figure 3. Altering VSD-pore coupling directly, by the mutation F351A, changes the gating permeation, and pharmacology of KCNQ1 channels.(A) VCF recordings from oocytes expressing pseudo-WT/F351A (C214A/G219C/C331A/F351A), labeled with Alexa 488 C5-maleimide. Left–GV (red) and FV (solid green) relationships with the main and high voltage FV components plotted (dotted green lines). Right–normalized fluorescence (green) and current (red) responses to a 60 mV pulse, the current from a cell expressing pseudo-WT KCNQ1+KCNE1 is shown for comparison (grey). (B) Left–currents from a single oocyte expressing F351A in external solutions containing 100 mM of Na+, K+, or Rb+. Right–averaged Rb+/K+ permeability ratios for WT KCNQ1 (black) and F351A (red). (C) Left–currents from an oocyte expressing F351A in control and 5 μM XE991 external solutions. Middle–time dependence of XE991 inhibition—the averaged ratio of the current in 5 μM XE991 to that in control solutions is plotted vs depolarization time. Right–averaged fraction inhibited after 200 (dashed line), 500 (thin line) or 2000 (thick line) ms of depolarization is plotted vs concentration of XE991 for oocytes expressing WT KCNQ1 (black), F351A (red), or WT KCNQ1+KCNE1 (grey).DOI: http://dx.doi.org/10.7554/eLife.03606.011
	Figure 4. KCNE1 increases the apparent affinity of the activated-open state for PIP2.(A) Responses of currents from oocytes expressing E1R/R4E alone (left) or E1R/R4E+KCNE1 (middle) to rapid depletion of PIP2 by CiVSP (VSP, blue). The membrane voltage was pulsed to +60 mV to activate CiVSP. Currents were normalized to the value 200 ms after depolarization for comparison with currents from oocytes not expressing CiVSP (black = channel subunits alone, blue = channel subunits + CiVSP). Right–averaged current responses for oocytes expressing E1R/R4E+CiVSP (−KCNE1) or E1R/R4E+KCNE1+CiVSP (+KCNE1). (B) CiVSP responses (VSP, blue) of currents from oocytes expressing WT KCNQ1 or WT KCNQ1+KCNE1. Two +80 mV depolarizing pulses were applied, spaced 30 s apart (note: time scale is broken). The currents were normalized to the value 200 ms into the first depolarizing pulse for comparison with currents from an oocyte expressing channel subunits alone (black). (C) Left–double pulse protocol in which two 25 s depolarizing pulses were applied. In between the two pulses the membrane potential was set to various voltages for 10 s. After each sweep, the membrane potential was held at −80 mV for 300 s to deactivate CiVSP and allow for PIP2 regeneration by the endogenous lipid kinases. Middle–currents from an oocyte expressing KCNQ1+KCNE1+CiVSP subjected to the voltage protocol shown and normalized to the value at the end of the first pulse (I1). Right–fraction of the first pulse current available on the second pulse (I2/I1) is plotted vs voltage of intervening 10 s (blue). The voltage-dependence of I2/I1 (solid blue line) is similar to that of the GV relationship for WT KCNQ1+KCNE1 (dotted black line) suggesting that the open probability during the 10 second interpulse determines the unbinding of PIP2.DOI: http://dx.doi.org/10.7554/eLife.03606.012
	Figure 5. Modeling the effects of KCNE1.(A) Cartoon illustrating the observed effects of KCNE1 on KCNQ1. The VSDs transit between resting (R, grey patterned), intermediate (I, red patterned), and activated (A, blue patterned) states. Each VSD conformation has unique interactions (double arrow) with the closed (C) and open (O) conformation of the pore. KCNE1 suppresses the intermediate-open (OI) state and modulates the activated-open (OA) states. (B) Kinetic model of KCNQ1 channel gating where the k parameters are the intrinsic transition rates of the VSD and the pore, and the θ parameters explicitly represent VSD-pore interactions. Fourth power notation ([ ]4) indicates that the model includes four VSDs. (C and D) Experimental data and model simulations with (+KCNE1) and without KCNE1. Steady-state current- (C, top), conductance- (C, middle), and fluorescence- (C, bottom) voltage relationships. (D) Current (black) and fluorescence (green) responses at various voltages.DOI: http://dx.doi.org/10.7554/eLife.03606.013Figure 5—figure supplement 1. Scheme for voltage-depedendent gating.The channel is modeled as a pore coupled to four voltage-sensing domains. VSD activation occurs in two transitions, resting (R) to intermediate (I) along the horizontal and intermediate to activated (A) along the vertical. The pore can be fully closed (C, back face, grey) or fully open (O, front face, black), with any combination of VSD-states. The state-notation indicates the conformation of the pore and the combination of the four VSDs (subscripted). For example CRRRR indicates the state where the pore is closed and all four VSDs are resting.DOI: http://dx.doi.org/10.7554/eLife.03606.014
	Figure 5—figure supplement 2. Balanced gating model showing transition rates.As described in the text the k parameters represent the intrinsic rates of the two domains and the θ parameters represent the effect of VSD-pore interactions at different states. The closed to open transitions dependent on the intrinsic rate of the pore (kco) divided by the closed state interactions with the VSDs. The open to closed transitions depend on the koc divided by the open state interactions the VSDs. n(X) indiciated the number of VSDs in state X.DOI: http://dx.doi.org/10.7554/eLife.03606.015
	Figure 5—figure supplement 3. Desriptions, values and units for free parameters of gating model.The values represent those used in the kinetic modeling of KCNQ1 gating. ΔKCNE1 column indicates the changes used to simulate the effects of KCNE1 on KCNQ1 channel gating.DOI: http://dx.doi.org/10.7554/eLife.03606.016
	Figure 5—figure supplement 4. Descriptions, values, and units for constant parameters used in gating model simulation.DOI: http://dx.doi.org/10.7554/eLife.03606.017

Bagnéris, Role of the C-terminal domain in the structure and function of tetrameric sodium channels. 2013, Pubmed

Bagnéris, Role of the C-terminal domain in the structure and function of tetrameric sodium channels. 2013, Pubmed
Barhanin, K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. 1996, Pubmed , Xenbase
Barro-Soria, KCNE1 divides the voltage sensor movement in KCNQ1/KCNE1 channels into two steps. 2014, Pubmed
Blumenthal, The minK potassium channel exists in functional and nonfunctional forms when expressed in the plasma membrane of Xenopus oocytes. 1994, Pubmed , Xenbase
Boulet, Role of the S6 C-terminus in KCNQ1 channel gating. 2007, Pubmed
Chan, Characterization of KCNQ1 atrial fibrillation mutations reveals distinct dependence on KCNE1. 2012, Pubmed
Chapman, Activation-dependent subconductance levels in the drk1 K channel suggest a subunit basis for ion permeation and gating. 1997, Pubmed , Xenbase
Chen, The S4-S5 linker couples voltage sensing and activation of pacemaker channels. 2001, Pubmed , Xenbase
Chen, Charybdotoxin binding in the I(Ks) pore demonstrates two MinK subunits in each channel complex. 2003, Pubmed , Xenbase
Chen, Structure of the full-length Shaker potassium channel Kv1.2 by normal-mode-based X-ray crystallographic refinement. 2010, Pubmed
Chung, Location of KCNE1 relative to KCNQ1 in the I(KS) potassium channel by disulfide cross-linking of substituted cysteines. 2009, Pubmed
Cui, Gating of IsK expressed in Xenopus oocytes depends on the amount of mRNA injected. 1994, Pubmed , Xenbase
Delemotte, Intermediate states of the Kv1.2 voltage sensor from atomistic molecular dynamics simulations. 2011, Pubmed
Eswar, Comparative protein structure modeling using MODELLER. 2007, Pubmed
Falkenburger, Kinetics of PIP2 metabolism and KCNQ2/3 channel regulation studied with a voltage-sensitive phosphatase in living cells. 2010, Pubmed
Goldstein, Site-specific mutations in a minimal voltage-dependent K+ channel alter ion selectivity and open-channel block. 1991, Pubmed , Xenbase
HODGKIN, A quantitative description of membrane current and its application to conduction and excitation in nerve. 1952, Pubmed
Haddad, Mode shift of the voltage sensors in Shaker K+ channels is caused by energetic coupling to the pore domain. 2011, Pubmed , Xenbase
Haitin, Intracellular domains interactions and gated motions of I(KS) potassium channel subunits. 2009, Pubmed , Xenbase
Hedley, The genetic basis of long QT and short QT syndromes: a mutation update. 2009, Pubmed
Horrigan, Allosteric voltage gating of potassium channels I. Mslo ionic currents in the absence of Ca(2+). 1999, Pubmed , Xenbase
Iwasaki, A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN, dephosphorylates phosphatidylinositol 4,5-bisphosphate. 2008, Pubmed , Xenbase
Jensen, Mechanism of voltage gating in potassium channels. 2012, Pubmed
Jiang, The open pore conformation of potassium channels. 2002, Pubmed
Kang, Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel. 2008, Pubmed
Kasimova, PIP₂-dependent coupling is prominent in Kv7.1 due to weakened interactions between S4-S5 and S6. 2015, Pubmed
Kurokawa, TEA(+)-sensitive KCNQ1 constructs reveal pore-independent access to KCNE1 in assembled I(Ks) channels. 2001, Pubmed
Lacroix, Intermediate state trapping of a voltage sensor. 2012, Pubmed , Xenbase
Larsson, Transmembrane movement of the shaker K+ channel S4. 1996, Pubmed , Xenbase
Lee, Two separate interfaces between the voltage sensor and pore are required for the function of voltage-dependent K(+) channels. 2009, Pubmed , Xenbase
Li, KCNE1 enhances phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity of IKs to modulate channel activity. 2011, Pubmed , Xenbase
Liu, Gated access to the pore of a voltage-dependent K+ channel. 1997, Pubmed
Long, Voltage sensor of Kv1.2: structural basis of electromechanical coupling. 2005, Pubmed
Long, Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment. 2007, Pubmed
Loussouarn, Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels. 2003, Pubmed
Lu, Coupling between voltage sensors and activation gate in voltage-gated K+ channels. 2002, Pubmed , Xenbase
Lu, Ion conduction pore is conserved among potassium channels. 2001, Pubmed
Lundby, Structural basis for K(V)7.1-KCNE(x) interactions in the I(Ks) channel complex. 2010, Pubmed
Lvov, Identification of a protein-protein interaction between KCNE1 and the activation gate machinery of KCNQ1. 2010, Pubmed
Mannuzzu, Direct physical measure of conformational rearrangement underlying potassium channel gating. 1996, Pubmed , Xenbase
Morin, Counting membrane-embedded KCNE beta-subunits in functioning K+ channel complexes. 2008, Pubmed , Xenbase
Nakajo, KCNE1 and KCNE3 stabilize and/or slow voltage sensing S4 segment of KCNQ1 channel. 2007, Pubmed , Xenbase
Nakajo, Stoichiometry of the KCNQ1 - KCNE1 ion channel complex. 2010, Pubmed , Xenbase
Osteen, KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate. 2010, Pubmed , Xenbase
Osteen, Allosteric gating mechanism underlies the flexible gating of KCNQ1 potassium channels. 2012, Pubmed , Xenbase
Paavonen, Response of the QT interval to mental and physical stress in types LQT1 and LQT2 of the long QT syndrome. 2001, Pubmed
Papazian, Electrostatic interactions of S4 voltage sensor in Shaker K+ channel. 1995, Pubmed , Xenbase
Payandeh, Crystal structure of a voltage-gated sodium channel in two potentially inactivated states. 2012, Pubmed
Plant, Individual IKs channels at the surface of mammalian cells contain two KCNE1 accessory subunits. 2014, Pubmed
Pusch, Gating and flickery block differentially affected by rubidium in homomeric KCNQ1 and heteromeric KCNQ1/KCNE1 potassium channels. 2000, Pubmed , Xenbase
Pusch, Activation and inactivation of homomeric KvLQT1 potassium channels. 1998, Pubmed , Xenbase
Rocheleau, KCNE peptides differently affect voltage sensor equilibrium and equilibration rates in KCNQ1 K+ channels. 2008, Pubmed , Xenbase
Ruscic, IKs channels open slowly because KCNE1 accessory subunits slow the movement of S4 voltage sensors in KCNQ1 pore-forming subunits. 2013, Pubmed
Sanguinetti, Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. 1996, Pubmed , Xenbase
Schoppa, The size of gating charge in wild-type and mutant Shaker potassium channels. 1992, Pubmed
Schwartz, Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias. 2001, Pubmed
Sesti, Single-channel characteristics of wild-type IKs channels and channels formed with two minK mutants that cause long QT syndrome. 1998, Pubmed , Xenbase
Shamgar, KCNE1 constrains the voltage sensor of Kv7.1 K+ channels. 2008, Pubmed , Xenbase
Silva, A multiscale model linking ion-channel molecular dynamics and electrostatics to the cardiac action potential. 2009, Pubmed
Silva, Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve. 2005, Pubmed
Smart, HOLE: a program for the analysis of the pore dimensions of ion channel structural models. 1996, Pubmed
Strutz-Seebohm, Structural basis of slow activation gating in the cardiac I Ks channel complex. 2011, Pubmed , Xenbase
Sun, Regulation of Voltage-Activated K(+) Channel Gating by Transmembrane β Subunits. 2012, Pubmed
Tai, The conduction pore of a cardiac potassium channel. 1998, Pubmed , Xenbase
Tapper, Location and orientation of minK within the I(Ks) potassium channel complex. 2001, Pubmed , Xenbase
Tiwari-Woodruff, Electrostatic interactions between transmembrane segments mediate folding of Shaker K+ channel subunits. 1997, Pubmed , Xenbase
Tristani-Firouzi, Voltage-dependent inactivation of the human K+ channel KvLQT1 is eliminated by association with minimal K+ channel (minK) subunits. 1998, Pubmed , Xenbase
Tristani-Firouzi, Interactions between S4-S5 linker and S6 transmembrane domain modulate gating of HERG K+ channels. 2002, Pubmed , Xenbase
Wang, MinK residues line a potassium channel pore. 1996, Pubmed
Wang, Subunit composition of minK potassium channels. 1995, Pubmed , Xenbase
Wang, Molecular basis for differential sensitivity of KCNQ and I(Ks) channels to the cognitive enhancer XE991. 2000, Pubmed , Xenbase
Wang, MinK-KvLQT1 fusion proteins, evidence for multiple stoichiometries of the assembled IsK channel. 1998, Pubmed
Wang, Gating-related molecular motions in the extracellular domain of the IKs channel: implications for IKs channelopathy. 2011, Pubmed , Xenbase
Webster, Intracellular gate opening in Shaker K+ channels defined by high-affinity metal bridges. 2004, Pubmed
Wrobel, The KCNE Tango - How KCNE1 Interacts with Kv7.1. 2012, Pubmed
Wu, State-dependent electrostatic interactions of S4 arginines with E1 in S2 during Kv7.1 activation. 2010, Pubmed , Xenbase
Wu, KCNE1 remodels the voltage sensor of Kv7.1 to modulate channel function. 2010, Pubmed , Xenbase
Xu, KCNQ1 and KCNE1 in the IKs channel complex make state-dependent contacts in their extracellular domains. 2008, Pubmed , Xenbase
Xu, Building KCNQ1/KCNE1 channel models and probing their interactions by molecular-dynamics simulations. 2013, Pubmed
Yang, Single-channel properties of IKs potassium channels. 1998, Pubmed , Xenbase
Zagotta, Shaker potassium channel gating. III: Evaluation of kinetic models for activation. 1994, Pubmed , Xenbase
Zaydman, Kv7.1 ion channels require a lipid to couple voltage sensing to pore opening. 2013, Pubmed , Xenbase
Zaydman, PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid modulation of voltage-dependent gating. 2014, Pubmed
Zhang, PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents. 2003, Pubmed , Xenbase
Zhang, Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel. 2012, Pubmed
Zhou, Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution. 2001, Pubmed
del Camino, Tight steric closure at the intracellular activation gate of a voltage-gated K(+) channel. 2001, Pubmed