首页> 外文期刊>Life sciences >Decreased expression of small-conductance Ca2+-activated K+ channels SK1 and SK2 in human chronic atrial fibrillation.
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Decreased expression of small-conductance Ca2+-activated K+ channels SK1 and SK2 in human chronic atrial fibrillation.

机译:在人类慢性心房颤动中小传导性Ca2 +激活的K +通道SK1和SK2的表达降低。

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摘要

Small-conductance Ca2+-activated K+ (SK) channels are recognized as new ion channel candidates in atrial fibrillation (AF), with pivotal implications as novel drug targets due to their atrial-selective distribution in humans. The purpose of this study was to investigate whether SK channels and the Ca2+-activated K+ current (IK,Ca) are involved in electrical remodeling of human chronic AF (cAF) and whether they display the differential distribution between the right (RA) and left atria (LA).The right (RAA) and left atrial appendage (LAA) myocytes were obtained from 29 sinus rhythm (SR) and 22 cAF patients. The IK,Ca and action potential (AP) were recorded using the patch-clamp technique. Three SK channel subtypes (SK1-3) expressions were assayed by western blot and real-time quantitative PCR analysis.The IK,Ca was decreased and its role in AP repolarization was attenuated in cAF, concomitant with a significant decrease in protein and mRNA levels of SK1 and SK2. In either SR or cAF, there was no difference in the IK,Ca density and protein and mRNA expression levels of SK1-3 between RAA and LAA myocytes.Our results demonstrated that SK1 and SK2 are involved in electrical remodeling of cAF. SK1-3 and IK,Ca do not display the inter-atrial differential distribution in SR or cAF. These findings provide a new insight into mechanisms of electrical remodeling of human cAF.
机译:小传导性Ca2 +激活的K +(SK)通道被认为是房颤(AF)中新的离子通道候选者,由于它们在人体内的心房选择性分布,其作为新型药物靶点具有关键意义。这项研究的目的是调查SK通道和Ca2 +激活的K +电流(IK,Ca)是否参与人类慢性AF(cAF)的电重构,以及它们是否显示出右侧(RA)和左侧的差异分布心房(LA)。右(RAA)和左心耳(LAA)心肌细胞来自29窦性心律(SR)和22 cAF患者。使用膜片钳技术记录IK,Ca和动作电位(AP)。通过Western blot和实时定量PCR分析了三种SK通道亚型(SK1-3)的表达。在CAF中,IK,Ca减少​​,其在AP复极中的作用减弱,同时蛋白质和mRNA水平显着降低SK1和SK2。在SR或cAF中,RAA和LAA心肌细胞的IK,Ca密度以及SK1-3的蛋白质和mRNA表达水平没有差异。我们的结果表明,SK1和SK2参与了cAF的电重构。 SK1-3和IK,Ca在SR或cAF中不显示房间差异分布。这些发现为人类cAF的电重构机制提供了新的见识。

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