Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation.
Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation.
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DOI：
10.1161/01.res.80.6.772
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发表时间：
1997-06
影响因子：
20.1
通讯作者：
D. R. Wagoner;Amber L. Pond;P. McCarthy;J. Trimmer;J. Nerbonne
中科院分区：
文献类型：
--
作者：
D. R. Wagoner;Amber L. Pond;P. McCarthy;J. Trimmer;J. Nerbonne
慢性心房颤动与心房动作电位持续时间和心房不应期缩短有关。为了验证这些变化是由特定心房K+电流密度变化介导的假设，我们比较了正常窦性心律患者（n = 28）和慢性心房颤动（AF）患者（n = 15）左右心房附件中左右心房肌细胞的K+电流密度和延迟整流K+通道α亚基蛋白（Kv1.5和Kv2.1）的密度。与我们的预期相反，ny抑素穿孔补片记录的全细胞K+电流显示，相对于正常窦性心律患者分离的左心房和右心房肌细胞的ITO和IKsus密度，慢性房颤患者分离的左心房和右心房肌细胞的ITO和IKsus密度显著降低。定量Western blot分析显示，虽然Kv2.1蛋白的表达没有变化，但Kv1.5蛋白的表达在房颤患者左、右心房附件中均降低了50%。Kv1.5的表达与延迟整流K+电流密度的降低并行，这一发现与最近的建议一致，即Kv1.5是人类心房肌细胞延迟整流K+电流的主要组成部分，超快速延迟整流K+电流IKur。房颤患者心房肌细胞中电压门控外向K+电流密度的意外发现表明，需要进一步研究房颤期间发生的电生理重构的细节，以便制定更有效和更安全的治疗策略。
Chronic atrial fibrillation is associated with a shortening of the atrial action potential duration and atrial refractory period. To test the hypothesis that these changes are mediated by changes in the density of specific atrial K+ currents, we compared the density of K+ currents in left and right atrial myocytes and the density of delayed rectifier K+ channel alpha-subunit proteins (Kv1.5 and Kv2.1) in left and right atrial appendages from patients (n = 28) in normal sinus rhythm with those from patients (n = 15) in chronic atrial fibrillation (AF). Contrary to our expectations, nystatin-perforated patch recordings of whole-cell K+ currents revealed significant reductions in both the inactivating (ITO) and sustained (IKsus) outward K+ current densities in left and right atrial myocytes isolated from patients in chronic AF, relative to the ITO and IKsus densities in myocytes isolated from patients in normal sinus rhythm. Quantitative Western blot analysis revealed that although there was no change in the expression of the Kv2.1 protein, the expression of Kv1.5 protein was reduced by > 50% in both the left and the right atrial appendages of AF patients. The finding that Kv1.5 expression is reduced in parallel with the reduction in delayed rectifier K+ current density is consistent with recent suggestions that Kv1.5 underlies the major component of the delayed rectifier K+ current in human atrial myocytes, the ultrarapid delayed rectifier K+ current, IKur. The unexpected finding of reduced voltage-gated outward K+ current densities in atrial myocytes from AF patients demonstrates the need to further examine the details of the electrophysiological remodeling that occurs during AF to enable more effective and safer therapeutic strategies to be developed.