Response to Letter Regarding Article, "Upregulation of K2P3.1 K+ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation".
Response to Letter Regarding Article, "Upregulation of K2P3.1 K+ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation".
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对有关文章“K2P3.1 K 电流上调导致慢性心房颤动患者动作电位缩短”的信件的回复。
作者：
C. Schmidt;F. Wiedmann;N. Voigt;Xiaobo Zhou;J. Heijman;S. Lang;V. Albert;S. Kallenberger;A. Ruhparwar;G. Szabó;K. Kallenbach;M. Karck;M. Borggrefe;P. Biliczki;J. Ehrlich;I. Baczkó;P. Lugenbiel;P. Schweizer;B. Donner;H. Katus;D. Dobrev;Dierk Thomas
我们感谢Olschewski博士及其同事对我们的文章的兴趣，1我们感谢他们对我们工作的2个关键发现的概括：（1）在慢性房颤（AF）患者中，心房K2P3.1（ASK-1）K+通道表达增加，IK2P3.1上调和动作电位缩短作为底物的鉴定;和（2）在心律失常的这一子实体中，将K2P3.1电流抑制和导致的动作电位延长作为基于机制的治疗范例。我们的研究重点是K2P3.1通道对人类心房电生理和动作电位调节的机制贡献，特别强调AF的病理生理失调。根据研究中提供的机制数据，通过抑制心房K2P3.1电流来功能纠正心房离子重构成为AF管理的一种新的抗心律失常选择。
我们同意Olschewski等人的观点，即在将新的治疗原则转移到人体应用之前，需要对疗效和安全性进行深入的临床前评价。在他们的信中，作者强调了他们对K2P3.1表达和功能的发现。
We thank Dr Olschewski and colleagues for their interest in our article,1 and we appreciate their recapitulation of 2 key findings of our work: (1) the identification of increased atrial K2P3.1 (TASK-1) K+ channel expression, I K2P3.1 upregulation, and action potential shortening as substrate in patients with chronic atrial fibrillation (AF); and (2) the presentation of K2P3.1 current inhibition and resulting action potential prolongation as mechanism-based therapeutic paradigm in this subentity of the arrhythmia. Our study focused on the mechanistic contribution of K2P3.1 channels to human atrial electrophysiology and action potential regulation, with particular emphasis on pathophysiological dysregulation in AF. Based on mechanistic data presented in the study, functional correction of atrial ionic remodeling through the suppression of atrial K2P3.1 current emerged as a novel antiarrhythmic option for AF management.
We agree with Olschewski et al that efficacy and safety require in-depth preclinical evaluation before transfer of novel therapeutic principles into human application. In their letter, the authors highlight their findings of K2P3.1 expression and functional …