Decreased ATP-sensitive K+ current density during chronic human atrial fibrillation
Decreased ATP-sensitive K+ current density during chronic human atrial fibrillation
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DOI：
10.1016/s0022-2828(03)00246-3
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发表时间：
2003-12-01
影响因子：
5
通讯作者：
Ravens, U
中科院分区：
文献类型：
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作者：
Balana, B;Dobrev, D;Ravens, U
慢性心房颤动（AF）与动作电位时程（APD）缩短有关，其涉及心房离子电流活性的改变。然而.对ATP敏感性K+通道的活性知之甚少（I-K，I-ATP）在慢性AE期间AF相关的1（K.ATP）将减少APD，并可能有助于AF的启动和/或持续。在这里，我们研究了1 K的活性，窦性心律（SR）患者心房肌细胞中的ATP和慢性AF人心房肌细胞分离自心房组织，所述心房组织得自进行心脏直视手术的患者。内向整流电流用全细胞膜片钳技术通过施加从-100到+40 mV（0.5 Hz）的去极化斜坡脉冲（1245 ms）来测量。I-K、I-ATP通道开放剂利马卡林（rilmakalim）激活I-K、I-ATP。内向整流I-K1和I-K，I-ATP通过它们对1 mM Ba ~（2+）的敏感性鉴定。AF患者（-100 mV：-14.8 +/- 1.3 pA/pF，n = 38/10（细胞/患者））和SR患者（-13.8 +/- 1.5 pA/pF，n = 33/16）的细胞之间的I-K1密度无差异。在两种类型的细胞中，rilmakalim以浓度依赖性方式（0.3-10 μ M）刺激I-K，I-ATP（定义为rilmakalim诱导电流）。然而，μ M rilmakalim对AF细胞I-K，I-ATP的最大激活作用小于SR细胞，（-100 mV时：-5.3 +/- 0.8 pA/pF，n = 22/7 vs. -11.2 +/- 2.9 pA/pF，n = 19/9;+40 mV时：+9.6 +/- 2.1 pA/pF。AF和SR分别为22/7 vs. +23.7 +/- 3.4 pA/pF，n = 19/9; P < 0.05）。只有主动脉瓣疾病和肺动脉高压被发现是独立的贡献者I-K，I-ATP电流密度。我们提供的证据表明，慢性AF与ATP敏感性K+电流的下调。这些变化可能为慢性房颤的电重构提供了额外的分子机制（C）2003 Elsevier Ltd.保留所有权利。
Chronic atrial fibrillation (AF) is associated with shortening of action potential duration (APD), which involves modified activity of atrial ion currents. However. little is known about the activity of ATP-sensitive K+ channels (I-K,I-ATP) during chronic AE An AF-related increase in the activity of 1(K.ATP) would reduce APD and could contribute to initiation and/or perpetuation of AF. Here, we studied the activity of 1K,ATP in atrial myocytes from patients with sinus rhythm (SR) and chronic AF Human atrial myocytes were isolated from atrial tissue obtained from patients undergoing open-heart surgery. Inward rectifier currents were measured with the whole-cell patch-clamp technique by applying a depolarizing ramp pulse (1245 ms) from -100 to +40 mV (0.5 Hz). I-K,I-ATP was activated with the I-K,I-ATP channel opener rilmakalim. The inward rectifier I-K1 and I-K,I-ATP were identified by their sensitivity to 1 mM Ba2+. Density of I-K1 did not differ between cells from patients with AF (at -100 mV: -14.8 +/- 1.3 pA/pF, n = 38/10 (cells/patients)) and SR (-13.8 +/- 1.5 pA/pF, n = 33/16). In both types of cells, rilmakalim stimulated I-K,I-ATP (defined as rilmakalim-inducible current) in a concentration-dependent manner (0.3-10 muM). However, maximum activation of I-K,I-ATP with muM rilmakalim was smaller in AF than in SR cells (at -100 mV: -5.3 +/- 0.8 pA/pF, n = 22/7 vs. -11.2 +/- 2.9 pA/pF, n = 19/9; at +40 mV: +9.6 +/- 2.1 pA/pF. it = 22/7 vs. +23.7 +/- 3.4 pA/pF, n = 19/9 for AF and SR, respectively; P < 0.05). Only aortic valve disease and pulmonary hypertension were found to be independent contributors to I-K,I-ATP current density. We provide evidence that chronic AF is associated with a downregulation of ATP-sensitive K+ currents. These changes may provide an additional molecular mechanism for electrical remodeling in chronic AF (C) 2003 Elsevier Ltd. All rights reserved.