| First Author | Bögeholz N | Year | 2016 |
| Journal | J Mol Cell Cardiol | Volume | 101 |
| Pages | 106-115 | PubMed ID | 27838371 |
| Mgi Jnum | J:254368 | Mgi Id | MGI:6102672 |
| Doi | 10.1016/j.yjmcc.2016.11.004 | Citation | Bogeholz N, et al. (2016) Triggered activity in atrial myocytes is influenced by Na(+)/Ca(2+) exchanger activity in genetically altered mice. J Mol Cell Cardiol 101:106-115 |
| abstractText | 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 (WTOE; WTKO). 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. WTOE and KO vs. WTKO. However, DADs triggered full spontaneous action potentials (sAP) significantly more often in OE vs. WTOE (ratio sAP/DAD: OE:0.18+/-0.05; WTOE:0.02+/-0.02; p<0.001). Using the same protocol, a DAD triggered an sAP by tendency less often in KO vs. WTKO (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. WTOE and decreased in KO vs. WTKO. 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. |
