Van Wagoner D R, Pond A L, McCarthy P M, Trimmer J S, Nerbonne J M
Department of Cardiology, Cleveland (Ohio) Clinic Foundation, USA.
Circ Res. 1997 Jun;80(6):772-81. doi: 10.1161/01.res.80.6.772.
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.
慢性心房颤动与心房动作电位时程缩短和心房不应期缩短相关。为了检验这些变化是由特定心房钾电流密度的改变介导的这一假说，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、右心房肌细胞中钾电流的密度，以及左、右心耳中延迟整流钾通道α亚基蛋白（Kv1.5和Kv2.1）的密度。与我们的预期相反，全细胞钾电流的制霉菌素穿孔膜片钳记录显示，相对于正常窦性心律患者分离的心肌细胞中的I TO和I Ksus密度，慢性AF患者分离的左、右心房肌细胞中失活（I TO）和持续（I Ksus）外向钾电流密度均显著降低。定量蛋白质免疫印迹分析显示，虽然Kv2.1蛋白的表达没有变化，但AF患者左、右心耳中Kv1.5蛋白的表达均降低了> 50%。Kv1.5表达与延迟整流钾电流密度降低平行的这一发现与最近的观点一致，即Kv1.5是人心房肌细胞中延迟整流钾电流、超快速延迟整流钾电流I Kur的主要成分。AF患者心房肌细胞中电压门控外向钾电流密度降低这一意外发现表明，需要进一步研究AF期间发生的电生理重塑细节，以便制定更有效、更安全的治疗策略。
