Calcium-Mediated DAD in Membrane Potentials and Triggered Activity in Atrial Myocytes of ETV1 f/f MyHC Cre/+ Mice
Research Square (Research Square)(2022)
Abstract
Abstract The E-twenty-six variant 1 (ETV1) -dependent transcriptome played an important role in atrial electrical and structural remodeling and the occurrence of atrial fibrillation,but the underlying mechenism of ETV1 in atrial fibrillation is unclear. In this study, cardiomyocyte-specific ETV1 knockout (ETV1f/fMyHCCre/+, ETV1-CKO) mice were constructed to observe the susceptibility to AF and the underlying mechanism in AF associated with ETV1-CKO mice. AF susceptibility was examined by intraesophageal burst pacing,induction of AF was increased obviously in ETV1-CKO mice than WT mice. Electrophysiology experiments indicated shortened APD50 and APD90, increased incidence of DADs, decreased density of ICa,L in ETV1-CKO mice. There was no difference in V1/2 INACT and V1/2 ACT, but a significantly longer duration of the recovery time after inactivation in the ETV1-CKO mice. The recording of intracellular Ca2+ showed that there was significantly increased in the frequency of calcium spark, Ca2+ transient amplitude, and proportion of SCaEs in ETV1-CKO mice. Reduction of Cav1.2 rather than NCX1 and SERCA2a, increase RyR2, p-RyR2 and CaMKII was reflected in ETV1-CKO group. This study demonstrates that the increase in calcium spark and SCaEs conresponding to Ca2+ transient amplitude that may trigger DAD in membrance potential in ETV1-CKO mice, thereby increasing the risk of AF.
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Key words
atrial myocytes,membrane potentials,calcium-mediated
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