亚基相互作用决定了IKs参与心脏复极化和复极化储备。
Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve.
作者信息
Silva Jonathan, Rudy Yoram
机构信息
Cardiac Bioelectricity and Arrhythmia Center, Washington University, St Louis, MO 63130-4899, USA.
出版信息
Circulation. 2005 Sep 6;112(10):1384-91. doi: 10.1161/CIRCULATIONAHA.105.543306. Epub 2005 Aug 29.
Abstract
BACKGROUND
The role of IKs, the slow delayed rectifier K+ current, in cardiac ventricular repolarization has been a subject of debate.
METHODS AND RESULTS
We develop a detailed Markov model of IKs and its alpha-subunit KCNQ1 and examine their kinetic properties during the cardiac ventricular action potential at different rates. We observe that interaction between KCNQ1 and KCNE1 (the beta-subunit) confers kinetic properties on IKs that make it suitable for participation in action potential repolarization and its adaptation to rate changes; in particular, the channel develops an available reserve of closed states near the open state that can open rapidly on demand.
CONCLUSIONS
Because of its ability to form an available reserve, IKs can function as a repolarization reserve when IKr, the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.
摘要
背景
缓慢延迟整流钾电流（IKs）在心室复极化中的作用一直存在争议。
方法与结果
我们构建了IKs及其α亚基KCNQ1的详细马尔可夫模型，并研究了它们在不同心率下心室动作电位期间的动力学特性。我们观察到，KCNQ1与KCNE1（β亚基）之间的相互作用赋予了IKs动力学特性，使其适合参与动作电位复极化及其对心率变化的适应性；特别是，该通道在开放状态附近形成了一个可利用的关闭状态储备，可根据需要迅速开放。
结论
由于能够形成可利用的储备，当快速延迟整流钾电流（IKr）因疾病或药物作用而降低时，IKs可作为复极化储备发挥作用，并可防止动作电位过度延长和致心律失常性早期后除极的发生。
相似文献
1
Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve.亚基相互作用决定了IKs参与心脏复极化和复极化储备。
Circulation. 2005 Sep 6;112(10):1384-91. doi: 10.1161/CIRCULATIONAHA.105.543306. Epub 2005 Aug 29.
2
Dynamic partnership between KCNQ1 and KCNE1 and influence on cardiac IKs current amplitude by KCNE2.KCNQ1与KCNE1之间的动态伙伴关系以及KCNE2对心脏IKs电流幅度的影响。
J Biol Chem. 2009 Jun 12;284(24):16452-16462. doi: 10.1074/jbc.M808262200. Epub 2009 Apr 16.
3
Calmodulin is essential for cardiac IKS channel gating and assembly: impaired function in long-QT mutations.钙调蛋白对于心脏IKS通道门控和组装至关重要：长QT突变中的功能受损。
Circ Res. 2006 Apr 28;98(8):1055-63. doi: 10.1161/01.RES.0000218979.40770.69. Epub 2006 Mar 23.
4
Paroxysmal beta-adrenergic receptor-mediated alterations in ventricular repolarization at rapid heart rates during inhibition of delayed rectifier currents.在延迟整流电流抑制期间，快速心率下阵发性β肾上腺素能受体介导的心室复极改变。
J Cardiovasc Pharmacol. 2009 Sep;54(3):253-62. doi: 10.1097/FJC.0b013e3181b2b706.
5
Two components of delayed rectifier K+ current in heart: molecular basis, functional diversity, and contribution to repolarization.心脏中延迟整流钾电流的两个组成部分：分子基础、功能多样性及其对复极化的作用。
Acta Pharmacol Sin. 2004 Feb;25(2):137-45.
6
Slow delayed rectifier potassium current blockade contributes importantly to drug-induced long QT syndrome.缓慢延迟整流钾电流阻滞对药物引起的长 QT 综合征有重要贡献。
Circ Arrhythm Electrophysiol. 2013 Oct;6(5):1002-9. doi: 10.1161/CIRCEP.113.000239. Epub 2013 Aug 31.
7
Rb+ efflux through functional activation of cardiac KCNQ1/minK channels by the benzodiazepine R-L3 (L-364,373).通过苯二氮䓬类药物R-L3（L-364,373）对心脏KCNQ1/minK通道的功能激活实现铷离子外流。
Assay Drug Dev Technol. 2006 Aug;4(4):443-50. doi: 10.1089/adt.2006.4.443.
8
Mutation of colocalized residues of the pore helix and transmembrane segments S5 and S6 disrupt deactivation and modify inactivation of KCNQ1 K+ channels.孔螺旋以及跨膜片段S5和S6共定位残基的突变会破坏KCNQ1钾离子通道的失活并改变其失活状态。
J Physiol. 2005 Mar 1;563(Pt 2):359-68. doi: 10.1113/jphysiol.2004.080887. Epub 2005 Jan 13.
9
BACE1 modulates gating of KCNQ1 (Kv7.1) and cardiac delayed rectifier KCNQ1/KCNE1 (IKs).β-分泌酶1（BACE1）调节钾通道蛋白KCNQ1（Kv7.1）以及心脏延迟整流钾通道KCNQ1/KCNE1（IKs）的门控。
J Mol Cell Cardiol. 2015 Dec;89(Pt B):335-48. doi: 10.1016/j.yjmcc.2015.10.006. Epub 2015 Oct 8.
10
Restricting excessive cardiac action potential and QT prolongation: a vital role for IKs in human ventricular muscle.限制过度的心脏动作电位和QT间期延长：IKs在人心室肌中的重要作用。
Circulation. 2005 Sep 6;112(10):1392-9. doi: 10.1161/CIRCULATIONAHA.105.550111. Epub 2005 Aug 29.
引用本文的文献
1
Using Bayesian priors to overcome non-identifiablility issues in Hidden Markov models.使用贝叶斯先验来克服隐马尔可夫模型中的不可识别性问题。
bioRxiv. 2025 May 5:2024.04.20.590387. doi: 10.1101/2024.04.20.590387.
2
Targeting the I Channel PKA Phosphorylation Axis to Restore Its Function in High-Risk LQT1 Variants.靶向 I 通道 PKA 磷酸化轴以恢复其在高风险 LQT1 变异体中的功能。
Circ Res. 2024 Sep 13;135(7):722-738. doi: 10.1161/CIRCRESAHA.124.325009. Epub 2024 Aug 21.
3
Neurocardiac pathologies associated with potassium channelopathies.与钾通道病相关的神经心脏病理学。
Epilepsia. 2024 Sep;65(9):2537-2552. doi: 10.1111/epi.18066. Epub 2024 Aug 1.
4
Evaluating sequential and allosteric activation models in IKs channels with mutated voltage sensors.评估电压感受器突变的 IKs 通道的顺序和别构激活模型。
J Gen Physiol. 2024 Mar 4;156(3). doi: 10.1085/jgp.202313465. Epub 2024 Jan 31.
5
Emerging methods to model cardiac ion channel and myocyte electrophysiology.用于模拟心脏离子通道和心肌细胞电生理学的新兴方法。
Biophys Rev (Melville). 2023 Mar;4(1):011315. doi: 10.1063/5.0127713. Epub 2023 Mar 30.
6
Modeling the kinetics of heteromeric potassium channels.异源钾通道动力学建模。
Front Cell Neurosci. 2022 Nov 10;16:1036813. doi: 10.3389/fncel.2022.1036813. eCollection 2022.
7
Electrophysiology.电生理学
Commun Pure Appl Math. 2013 Dec;66(12):1837-1913. doi: 10.1002/cpa.21484. Epub 2013 Oct 9.
8
Bifurcations and Proarrhythmic Behaviors in Cardiac Electrical Excitations.心脏电兴奋中的分岔与致心律失常行为。
Biomolecules. 2022 Mar 16;12(3):459. doi: 10.3390/biom12030459.
9
Modulating the voltage sensor of a cardiac potassium channel shows antiarrhythmic effects.调节心脏钾通道的电压传感器可显示抗心律失常作用。
Proc Natl Acad Sci U S A. 2021 May 18;118(20). doi: 10.1073/pnas.2024215118.
10
Gating and Regulation of KCNQ1 and KCNQ1 + KCNE1 Channel Complexes.KCNQ1及KCNQ1 + KCNE1通道复合体的门控与调节
Front Physiol. 2020 Jun 4;11:504. doi: 10.3389/fphys.2020.00504. eCollection 2020.
本文引用的文献
1
Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model.犬心室肌细胞模型中动作电位和钙瞬变的频率依赖性及调节
Circulation. 2004 Nov 16;110(20):3168-74. doi: 10.1161/01.CIR.0000147231.69595.D3. Epub 2004 Oct 25.
2
Drug-induced prolongation of the QT interval.药物引起的QT间期延长。
N Engl J Med. 2004 Mar 4;350(10):1013-22. doi: 10.1056/NEJMra032426.
3
Modeling beta-adrenergic control of cardiac myocyte contractility in silico.在计算机模拟中对心肌细胞收缩性的β-肾上腺素能控制进行建模。
J Biol Chem. 2003 Nov 28;278(48):47997-8003. doi: 10.1074/jbc.M308362200. Epub 2003 Sep 12.
4
Accumulation of slowly activating delayed rectifier potassium current (IKs) in canine ventricular myocytes.犬心室肌细胞中缓慢激活延迟整流钾电流（IKs）的积累。
J Physiol. 2003 Sep 15;551(Pt 3):777-86. doi: 10.1113/jphysiol.2003.044040. Epub 2003 Jun 20.
5
Probing the contribution of IKs to canine ventricular repolarization: key role for beta-adrenergic receptor stimulation.探究IKs对犬心室复极的贡献：β-肾上腺素能受体刺激的关键作用。
Circulation. 2003 Jun 3;107(21):2753-60. doi: 10.1161/01.CIR.0000068344.54010.B3. Epub 2003 May 19.
6
Cardiac-enriched LIM domain protein fhl2 is required to generate I(Ks) in a heterologous system.心脏富集的LIM结构域蛋白Fhl2是在异源系统中产生I(Ks)所必需的。
Cardiovasc Res. 2002 Oct;56(1):93-103. doi: 10.1016/s0008-6363(02)00498-4.
7
Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel.KCNQ1-KCNE1钾通道β肾上腺素能受体调节所需的大分子信号复合物
Science. 2002 Jan 18;295(5554):496-9. doi: 10.1126/science.1066843.
8
Density and kinetics of I(Kr) and I(Ks) in guinea pig and rabbit ventricular myocytes explain different efficacy of I(Ks) blockade at high heart rate in guinea pig and rabbit: implications for arrhythmogenesis in humans.豚鼠和兔心室肌细胞中I(Kr)和I(Ks)的密度及动力学解释了I(Ks)阻滞剂在豚鼠和兔高心率时的不同疗效：对人类心律失常发生机制的启示
Circulation. 2001 Aug 21;104(8):951-6. doi: 10.1161/hc3401.093151.
9
Rate dependency of delayed rectifier currents during the guinea-pig ventricular action potential.豚鼠心室动作电位期间延迟整流电流的频率依赖性
J Physiol. 2001 Aug 1;534(Pt 3):721-32. doi: 10.1111/j.1469-7793.2001.00721.x.
10
The slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes.未患病人类心室肌细胞中延迟整流钾电流的缓慢成分。
Cardiovasc Res. 2001 Mar;49(4):790-7. doi: 10.1016/s0008-6363(00)00306-0.
Zotero 插件