An outwardly rectifying chloride channel in human atrial cardiomyocytes
An outwardly rectifying chloride channel in human atrial cardiomyocytes
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DOI：
10.1111/j.1540-8167.2005.00255.x
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发表时间：
2006-01-01
影响因子：
2.7
通讯作者：
Bois, P
中科院分区：
文献类型：
--
作者：
Demion, M;Guinamard, R;Bois, P
人心房心肌细胞中的ORCC。简介：在一系列氯离子通道中，已报道在各种物种的心脏中存在外向整流氯离子通道。虽然这个通道携带的阴离子电流已经受到强烈的电生理学调查，矛盾的是没有检查的单通道电流已报告为人类心肌细胞。方法和结果：使用膜片钳技术的细胞附着和无细胞配置，我们描述了外向整流氯离子电流（ORCC）的特性，在新鲜分离的人心房心肌细胞的单位水平。在切除的由内而外的斑块中，通道呈现非线性I/V关系，在正电压范围内电导为76.5 +/- 14.7 pS，在负电压范围内电导为8.1 +/- 2 pS，表明向外整流。与蛋白激酶C激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）的预孵育显着增加观察到的自发活动通道的数量。该通道具有Cl-选择性（Cl-/Na+渗透比，P-Cl/P-Na= 18），渗透性顺序为I- > Br- > Cl- > F- > glucose。它被经典的氯通道阻断剂格列本脲、NPPB、SITS和DIDS阻断。通道活性不依赖于内部钙离子浓度。在细胞贴附配置，ORCC通道激活下观察到灌注的低渗solution.Conclusion：人心房肌细胞表达一个外向整流的Cl-通道，是敏感的PKC激活。该通道与涉及心肌缺血和扩张性心脏病等心脏病理的肿胀激活氯电流具有生物物理和药理学特性。
ORCC in Human Atrial Cardiomyocytes. Introduction: Among a range of chloride channels, outwardly rectifying Cl- channels have been reported in the heart of various species. Although the anionic current carried by this channel has been subjected to intense electrophysiological investigations, paradoxically no examination of single-channel currents has been reported for human cardiomyocytes.Methods and Results: Using the cell-attached and cell-free configurations of the patch-clamp technique, we have characterized the properties of an outwardly rectifying chloride current (ORCC) at the unitary level in freshly isolated human atrial cardiomyocytes. In excised inside-out patches, the channel presented a nonlinear I/V relationship with a conductance of 76.5 +/- 14.7 pS in the positive voltage range and 8.1 +/- 2 pS in the negative voltage range, indicating an outward rectification. Preincubation with the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) significantly increased the number of spontaneously active channels observed. The channel was Cl- selective (Cl- to Na+ permeability ratio, P-Cl/P-Na= 18) with the permeability sequence I- > Br- > Cl- > F- > gluconate. It was blocked by the classical Cl- channels blockers glibenclamide, NPPB, SITS, and DIDS. Channel activity was not dependent upon internal calcium concentration. In the cell-attached configuration, ORCC channel activation was observed under perfusion of a hypotonic solution.Conclusion: Human atrial myocytes express an outwardly rectifying Cl- channel that is sensitive to PKC activation. This channel shares biophysical and pharmacological properties with the swelling-activated chloride current implicated in cardiac pathologies such as myocardial ischemia and dilated cardiopathies.