@article{MaurerHartmannArgyriouetal.2022,
  author    = {Maurer, Wiebke and Hartmann, Nico and Argyriou, Loukas and Sossalla, Samuel and Streckfuss-B{\"o}meke, Katrin},
  title     = {Generation of homozygous Na\(_{v}\)1.8 knock-out iPSC lines by CRISPR Cas9 genome editing to investigate a potential new antiarrhythmic strategy},
  series = {Stem Cell Research},
  volume    = {60},
  journal   = {Stem Cell Research},
  doi       = {10.1016/j.scr.2022.102677},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300936},
  year      = {2022},
  abstract  = {The sodium channel Na\(_{v}\)1.8, encoded by SCN10A, is reported to contribute to arrhythmogenesis by inducing the late I\(_{Na}\) and thereby enhanced persistent Na\(^{+}\) current. However, its exact electrophysiological role in cardiomyocytes remains unclear. Here, we generated induced pluripotent stem cells (iPSCs) with a homozygous SCN10A knock-out from a healthy iPSC line by CRISPR Cas9 genome editing. The edited iPSCs maintained full pluripotency, genomic integrity, and spontaneous in vitro differentiation capacity. The iPSCs are able to differentiate into iPSC-cardiomyocytes, hence making it possible to investigate the role of Na\(_{v}\)1.8 in the heart.},
  language  = {en}
}
@article{HartmannKnierimMaureretal.2023,
  author    = {Hartmann, Nico and Knierim, Maria and Maurer, Wiebke and Dybkova, Nataliya and Hasenfuß, Gerd and Sossalla, Samuel and Streckfuss-B{\"o}meke, Katrin},
  title     = {Molecular and functional relevance of Na\(_V\)1.8-induced atrial arrhythmogenic triggers in a human SCN10A knock-out stem cell model},
  series = {International Journal of Molecular Sciences},
  volume    = {24},
  journal   = {International Journal of Molecular Sciences},
  number    = {12},
  issn      = {1422-0067},
  doi       = {10.3390/ijms241210189},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362708},
  year      = {2023},
  abstract  = {In heart failure and atrial fibrillation, a persistent Na\(^+\) current (I\(_{NaL}\)) exerts detrimental effects on cellular electrophysiology and can induce arrhythmias. We have recently shown that Na\(_V\)1.8 contributes to arrhythmogenesis by inducing a I\(_{NaL}\). Genome-wide association studies indicate that mutations in the SCN10A gene (Na\(_V\)1.8) are associated with increased risk for arrhythmias, Brugada syndrome, and sudden cardiac death. However, the mediation of these Na\(_V\)1.8-related effects, whether through cardiac ganglia or cardiomyocytes, is still a subject of controversial discussion. We used CRISPR/Cas9 technology to generate homozygous atrial SCN10A-KO-iPSC-CMs. Ruptured-patch whole-cell patch-clamp was used to measure the I\(_{NaL}\) and action potential duration. Ca\(^{2+}\) measurements (Fluo 4-AM) were performed to analyze proarrhythmogenic diastolic SR Ca\(^{2+}\) leak. The I\(_{NaL}\) was significantly reduced in atrial SCN10A KO CMs as well as after specific pharmacological inhibition of Na\(_V\)1.8. No effects on atrial APD\(_{90}\) were detected in any groups. Both SCN10A KO and specific blockers of Na\(_V\)1.8 led to decreased Ca\(^{2+}\) spark frequency and a significant reduction of arrhythmogenic Ca\(^{2+}\) waves. Our experiments demonstrate that Na\(_V\)1.8 contributes to I\(_{NaL}\) formation in human atrial CMs and that Na\(_V\)1.8 inhibition modulates proarrhythmogenic triggers in human atrial CMs and therefore Na\(_V\)1.8 could be a new target for antiarrhythmic strategies.},
  language  = {en}
}