Late Sodium Current in Atrial Cardiomyocytes Contributes to the Induced and Spontaneous Atrial Fibrillation in Rabbit Hearts. Issue 4 (October 2020)

• Record Type: Journal Article
• Authors: Chu, Yanpeng; Yang, Qiaomei; Ren, Lu; Yu, Shandong; Liu, Zhipei; Chen, Ying; Wei, Xiaohong; Huang, Sihui; Song, Lv; Zhang, Peihua; Ma, Jihua; Wu, Lin
• Is Part Of: Journal of cardiovascular pharmacology. Volume 76:Issue 4(2020)
• Publication Date: 2020-10
• Subjects: atrial fibrillation -- monophasic action potential -- effective refractory period -- late sodium current -- atrial myocyte; Cardiovascular Diseases -- drug therapy -- Periodicals; Cardiovascular System -- drug effects -- Periodicals; Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular agents; Cardiovascular pharmacology; Periodicals; 615.7105
• DOI: 10.1097/FJC.0000000000000883
• Languages: English
• ISSNs: 0160-2446

Abstract

Abstract : Abstract: Increased late sodium current (INa ) induces long QT syndrome 3 with increased risk of atrial fibrillation (AF). The role of atrial late INa in the induction of AF and in the treatment of AF was determined in this study. AF parameters were measured in isolated rabbit hearts exposed to late INa enhancer and inhibitors. Late INa from isolated atrial and ventricular myocytes were measured using whole-cell patch-clamp techniques. We found that induced-AF by programmed S1 S2 stimulation and spontaneous episodes of AF were recorded in hearts exposed to either low (0.1–3 nM) or high (3–10 nM) concentrations of ATX-II (n = 10). Prolongations in atrial monophasic action potential duration at 90% completion of repolarization and effective refractory period by ATX-II (0.1–15 nM) were greater in hearts paced at slow than at fast rates (n = 5–10, P < 0.05). Both endogenous and ATX-II-enhanced late INa density were greater in atrial than that in ventricular myocytes (n = 9 and 8, P < 0.05). Eleclazine and ranolazine reduced AF window and AF burden in association with the inhibition of both endogenous and enhanced atrial late INa with half maximal inhibitory concentrations (IC50 ) of 1.14 and 9.78, and 0.94 and 8.31 μM, respectively. The IC50 s for eleclazine and ranolazine to inhibit peak INa were 20.67 and 101.79 μM, respectively, in atrial myocytes. In conclusion, enhanced late INa in atrial myocytes increases the susceptibility for AF. Inhibition of either endogenous or enhanced late INa, with increased atrial potency of drugs is feasible for the treatment of AF.