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Mechanisms Underlying the Dual Effect of Polyunsaturated Fatty Acid Analogs on Kv7.1.
Liin SI
,
Yazdi S
,
Ramentol R
,
Barro-Soria R
,
Larsson HP
.
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Polyunsaturated fatty acid (PUFA) analogs represent a new class of potential anti-arrhythmic KV7.1 and KV7.1+KCNE1 channel activators. In this study, we describe dual independent activating effects of negatively charged PUFA analogs on KV7.1 and KV7.1+KCNE1 that are dependent on discrete channel motifs. PUFA analogs are critically dependent on K326 in S6 of KV7.1 to increase the maximum conductance and critically dependent on specific S4 arginines in KV7.1 to shift the voltage dependence of channel opening toward negative voltages. Our findings provide insights into how KV7.1+KCNE1 activators may interact electrostatically both with the pore domain and the voltage-sensing domain to augment channel activity. We believe that the molecular understanding of how PUFA analogs induce dual independent activating effects is an important step toward the development of effective anti-arrhythmic drugs that target KV7.1 channels.
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996, Pubmed,
Xenbase
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
Best,
Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles.
2012,
Pubmed
Bezanilla,
Gating of Shaker K+ channels: II. The components of gating currents and a model of channel activation.
1994,
Pubmed
,
Xenbase
Börjesson,
Electrostatic tuning of cellular excitability.
2010,
Pubmed
,
Xenbase
Carvacho,
Intrinsic electrostatic potential in the BK channel pore: role in determining single channel conductance and block.
2008,
Pubmed
,
Xenbase
Chakrapani,
On the structural basis of modal gating behavior in K(+) channels.
2011,
Pubmed
Conti,
Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation.
2016,
Pubmed
,
Xenbase
Cordero-Morales,
A multipoint hydrogen-bond network underlying KcsA C-type inactivation.
2011,
Pubmed
,
Xenbase
Cui,
Voltage-Dependent Gating: Novel Insights from KCNQ1 Channels.
2016,
Pubmed
Demo,
Ion effects on gating of the Ca(2+)-activated K+ channel correlate with occupancy of the pore.
1992,
Pubmed
Eldstrom,
Microscopic mechanisms for long QT syndrome type 1 revealed by single-channel analysis of I(Ks) with S3 domain mutations in KCNQ1.
2015,
Pubmed
Farag,
Polyunsaturated fatty acids inhibit Kv1.4 by interacting with positively charged extracellular pore residues.
2016,
Pubmed
,
Xenbase
Gibor,
An inactivation gate in the selectivity filter of KCNQ1 potassium channels.
2007,
Pubmed
,
Xenbase
Goldenberg,
Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome.
2006,
Pubmed
Larsen,
Extracellular potassium inhibits Kv7.1 potassium channels by stabilizing an inactivated state.
2011,
Pubmed
,
Xenbase
Liin,
Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations.
2016,
Pubmed
,
Xenbase
Liin,
The KCNQ1 channel - remarkable flexibility in gating allows for functional versatility.
2015,
Pubmed
Liin,
Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel.
2015,
Pubmed
,
Xenbase
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
Murray,
Unnatural amino acid photo-crosslinking of the IKs channel complex demonstrates a KCNE1:KCNQ1 stoichiometry of up to 4:4.
2016,
Pubmed
Nakajo,
KCNQ1 channel modulation by KCNE proteins via the voltage-sensing domain.
2015,
Pubmed
Nakajo,
Stoichiometry of the KCNQ1 - KCNE1 ion channel complex.
2010,
Pubmed
,
Xenbase
Nerbonne,
Molecular physiology of cardiac repolarization.
2005,
Pubmed
Ottosson,
Drug-induced ion channel opening tuned by the voltage sensor charge profile.
2014,
Pubmed
,
Xenbase
Panaghie,
The role of S4 charges in voltage-dependent and voltage-independent KCNQ1 potassium channel complexes.
2007,
Pubmed
,
Xenbase
Plant,
Individual IKs channels at the surface of mammalian cells contain two KCNE1 accessory subunits.
2014,
Pubmed
Poveda,
Lipid modulation of ion channels through specific binding sites.
2014,
Pubmed
Pusch,
Gating and flickery block differentially affected by rubidium in homomeric KCNQ1 and heteromeric KCNQ1/KCNE1 potassium channels.
2000,
Pubmed
,
Xenbase
Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase
Seebohm,
Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels.
2003,
Pubmed
,
Xenbase
Sun,
Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.
2017,
Pubmed
,
Xenbase
Vanoye,
Distinct subdomains of the KCNQ1 S6 segment determine channel modulation by different KCNE subunits.
2009,
Pubmed
Wu,
KCNE1 remodels the voltage sensor of Kv7.1 to modulate channel function.
2010,
Pubmed
,
Xenbase
Zaydman,
Domain-domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel.
2014,
Pubmed
,
Xenbase
Zhou,
The occupancy of ions in the K+ selectivity filter: charge balance and coupling of ion binding to a protein conformational change underlie high conduction rates.
2003,
Pubmed
