Triggered activity in atrial myocytes is influenced by Na+/Ca2+ exchanger activity in genetically altered mice.

Abstract Aims In atrial fibrillation, increased function of the Na + /Ca 2 + -exchanger (NCX) is one among several electrical remodeling mechanisms. Methods/results Using the patch-clamp- and Ca 2 + imaging-methods, we investigated atrial myocytes from NCX-homozygous-overexpressor (OE)- and heterozygous-knockout (KO)-mice and their corresponding wildtypes (WT OE ; WT KO ). NCX mediated Ca 2 + extrusion capacity was reduced in KO and increased in OE. There was no evidence for structural or molecular remodeling. During a proarrhythmic pacing-protocol, the number of low amplitude delayed afterdepolarizations (DADs) was unaltered in OE vs. WT OE and KO vs. WT KO . However, DADs triggered full spontaneous action potentials (sAP) significantly more often in OE vs. WT OE (ratio sAP/DAD: OE:0.18 ± 0.05; WT OE :0.02 ± 0.02; p KO ( p  = 0.06) and significantly less often under a more aggressive proarrhythmic protocol (ratio sAP/DAD: KO:0.01 ± 0.003; WT KO: 0.12 ± 0.05; p  = 0.007). The DAD amplitude was increased in OE vs. WT OE and decreased in KO vs. WT KO . There were no differences in SR-Ca 2 + -load, the number of spontaneous Ca 2 + -release-events or IKACh/IK1. Conclusions Atrial myocytes with increased NCX expression exhibited increased vulnerability towards sAPs while atriomyocytes with reduced NCX expression were protected. The underlying mechanism consists of a modification of the DAD-amplitude by the level of NCX-activity. Thus, although the number of spontaneous Ca 2 + -releases and therefore DADs is unaltered, the higher DAD-amplitude in OE made a transgression of the voltage-threshold of an sAP more likely. These findings indicate that the level of NCX activity could influence triggered activity in atrial myocytes independent of possible remodeling processes.