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Ion current profiles in canine ventricular myocytes obtained by the “onion peeling” technique
Journal of Molecular and Cellular Cardiology ( IF 4.9 ) Pub Date : 2021-06-03 , DOI: 10.1016/j.yjmcc.2021.05.011
Balázs Horváth 1 , Dénes Kiss 2 , Csaba Dienes 2 , Tamás Hézső 2 , Zsigmond Kovács 2 , Norbert Szentandrássy 3 , János Almássy 2 , János Magyar 4 , Tamás Bányász 2 , Péter P Nánási 5
Affiliation  

The profiles of ion currents during the cardiac action potential can be visualized by the action potential voltage clamp technique. To obtain multiple ion current data from the same cell, the “onion peeling” technique, based on sequential pharmacological dissection of ion currents, has to be applied. Combination of the two methods allows recording of several ion current profiles from the same myocyte under largely physiological conditions. Using this approach, we have studied the densities and integrals of the major cardiac inward (ICa, INCX, INa-late) and outward (IKr, IKs, IK1) currents in canine ventricular cells and studied the correlation between them. For this purpose, ventricular cardiomyocytes of the dog were chosen because their electrophysiological properties are similar to those of human ones.

Significant positive correlation was observed between the density and integral of ICa and IKr, and positive correlation was found also between the integral of ICa and INCX. No further correlations were detected. The Ca2+-sensitivity of K+ currents was studied by comparing their parameters in the case of normal calcium homeostasis and following blockade of ICa. Out of the three K+ currents studied, only IKs was Ca2+-sensitive. The density and integral of IKs was significantly greater, while its time-to-peak value was shorter at normal Ca2+ cycling than following ICa blockade. No differences were detected for IKr or IK1 in this regard.

Present results indicate that the positive correlation between ICa and IKr prominently contribute to the balance between inward and outward fluxes during the action potential plateau in canine myocytes. The results also suggest that the profiles of cardiac ion currents have to be studied under physiological conditions, since their behavior may strongly be influenced by the intracellular Ca2+ homeostasis and the applied membrane potential protocol.



中文翻译:

通过“洋葱剥皮”技术获得的犬心室肌细胞中的离子电流分布

心脏动作电位期间的离子电流分布可以通过动作电位电压钳技术可视化。为了从同一细胞中获得多个离子电流数据,必须应用基于离子电流顺序药理学解剖的“洋葱剥皮”技术。这两种方法的组合允许在很大程度上在生理条件下记录来自同一肌细胞的几个离子电流分布。使用这种方法,我们研究了主要心脏向内 (I Ca , I NCX , I Na-late ) 和向外 (I Kr , I Ks , I K1 ) 的密度和积分) 犬心室细胞中的电流,并研究了它们之间的相关性。为此目的,选择了狗的心室心肌细胞,因为它们的电生理特性与人类相似。

I Ca和I Kr的密度与积分呈显着正相关,I Ca的积分与I NCX也呈正相关。没有检测到进一步的相关性。K +电流的 Ca 2+敏感性通过比较它们在正常钙稳态和 I Ca阻断情况下的参数来研究。在所研究的三种K +电流中,只有I Ks对Ca 2+敏感。I Ks的密度和积分明显更大,而在正常 Ca 2+下其峰值时间更短骑自行车比遵循 I Ca封锁。在这方面没有检测到 I Kr或 I K1的差异。

目前的结果表明,I Ca和 I Kr之间的正相关显着有助于犬肌细胞动作电位平台期间向内和向外通量之间的平衡。结果还表明,必须在生理条件下研究心脏离子电流的分布,因为它们的行为可能受到细胞内 Ca 2+稳态和应用膜电位方案的强烈影响。

更新日期:2021-06-03
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