Project description: 

Short-QT Syndrome is an inherited channelopathy, which leads to sudden cardiac death at young age. Several genes have been related to the short-QT syndrome phenotype including mutations in the SLC4A3 Gene. SLC4A3 encodes a bicarbonat/chloride-exchanger. An international research team including a leading participation of researchers from the Department of Cellular and Translational Physiology at the Ruhr-University-Bochum ran a studying in collaboration with further six research centers this project to understand how mutations in the SLC4A3 lead to short-QT syndrome and sudden cardiac death.
Researchers found that in patient specific cardiomyocytes, which where differentiated from induced pluripotent stem cells carrying mutations in the SLC4A3 gene, the intracellular pH value is increased, the action potential duration is shortened and the ion channel density of L-Type-calcium channel current and of the sodium-calcium-exchanger were altered. Furthermore, more arrhythmic-events were detected in short-QT syndrome cardiomyocytes.

For that project patient specific induced pluripotent stem cells were reprogrammed and differentiated to cardiomyocytes. The mutations in the SLC4A3 gene were corrected using CRISPR/CAS 9. Different anti-arrhythmic drugs like quinidine and sotalol were successfully tested prolonged the action potential duration and reduced arrhythmic events. These findings may help to personalize treatment in patients suffering from short-QT syndrome
 

Publication: 

Eur Heart J.2026, Jun 16; SLC4A3-related short QT syndrome assessed in human induced pluripotent stem cell-derived cardiomyocytes: mechanisms of ventricular arrhythmia and sudden cardiac death, Zenghui Meng, Boldizsar Kovacs, Chen Yan, Christina Hölscher, Saltanat Zhazykbayeva, Oliver Jarkas, ..., Nazha Hamdani, Xiaobo Zhou, Ardan M Saguner, Ibrahim Akin, Michael H Gollob, Ibrahim El-Battrawy

Paper: https://pubmed.ncbi.nlm.nih.gov/41780556/