Calcium‐mediated <scp>DAD</scp> in membrane potentials and triggered activity in atrial myocytes of <scp>ETV1^f</scp>^/<scp>^fMyHC^Cre</scp>^/+ mice

The E-twenty-six variant 1 (ETV1)-dependent transcriptome plays an important role in atrial electrical and structural remodelling and the occurrence of atrial fibrillation (AF), but the underlying mechanism of ETV1 in AF is unclear. In this study, cardiomyocyte-specific ETV1 knockout (ETV1^f/fMyHC^Cre/+, 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 I_Ca,L in ETV1-CKO mice. There was no difference in V_INACT,1/2 and V_ACT,1/2, 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 corresponding to Ca²⁺ transient amplitude may trigger DAD in membrane potential in ETV1-CKO mice, thereby increasing the risk of AF.