Abstract

that irregular ventricular activation alters ion channel expression and cellular electrophysiology. Methods:mRNA expression of ion channels and accessory subunits was examined in neonatal rat ventricular myocytes (NVCMs) paced either regularly or irregularly for 24 hours to simulate ventricular activation in sinus rhythm (SR) and AF respectively. Relevant transmembrane currents were measured after 96 hours of regular vs irregular pacing using whole cell patch clamp approach. LV myocardium from end-stage heart failure (ESHF) patients in SR and chronic AF undergoing cardiac transplantation also underwent mRNA expression studies as guided by results from the NVCMmodel. Results: Irregular pacing induced a 48% increase in NVCMmRNA expression of KCNA4. However, there was no difference in Ito current density across pacing strategies. Irregular pacing induced trivial changes in NVCM mRNAexpression for theNa channel SCN5A (11% reduction), and the Ca channels CACNA1C (19% increase), and CACNA1H (8% decrease). No differences were observed for ion channels CACNA1G, KCNQ1, KCNH2, KCND3, KCNJ2, and KCNJ11; accessory subunits KCNE1, KCNE2, KCNIP2, and ABCC9; and gap junction subunits GJA1 and GJA5. There were no differences in mRNA expression of SCN5A, CACNA1C, CACNA1H, or KCNA4 in LV myocardium from ESHF patients in AF vs SR. Conclusion: In an acute model, irregular ventricular a i a a

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