2026-05-21T23:11:46Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/268422025-12-18T13:01:55Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Fernandes, Vítor S author Caballero, Ricardo author Siguero-Álvarez, Marcos author Papoutsi, Tania author Gimeno-Blanes, Juan Ramón author Delpón, Eva author de la Pompa, José Luís author 2025 Mutations in MINDBOMB 1 (MIB1), encoding an E3 ubiquitin ligase of the NOTCH signaling pathway, cause left ventricular noncompaction cardiomyopathy (LVNC) in mice and humans, increasing the risk of arrhythmia and left ventricular dysfunction. This study aimed to investigate the effect of MIB1 mutations on cardiac electrical activity. We examined male Mib1flox;Tnnt2Cre mice, a disease model of LVNC, and wildtype littermates on the C57BL/6J genetic background. Our results demonstrate that the gap-junction protein connexin43 was delocalized from the intercalated disks to the lateral long axis of Mib1flox;Tnnt2Cre cardiomyocytes. Cardiomyocyte electrophysiology revealed an increase in the Na (INa) peak density at potentials between -50 and -30 mV in Mib1flox;Tnnt2Cre mice, with no changes in INa activation or inactivation kinetics. Mib1flox;Tnnt2Cre cardiomyocytes also showed decreases in outward K+ peak currents and currents at the end of depolarizing pulses at potentials ≥-10 mV and ≥-20 mV, respectively, and this was accompanied by a lower charge density at ≥-20 mV. Action potential duration was increased in Mib1flox;Tnnt2Cre cardiomyocytes. The cardiac stress, induced by swimming endurance training or β-adrenergic stimulation with isoproterenol, increases QTc duration in Mib1flox;Tnnt2Cre mice, accompanied by a decrease in T-wave amplitude and area. Swimming endurance training decreased heart rate in wildtype and Mib1flox;Tnnt2Cre mice but was unaffected by long-term isoproterenol treatment. These mouse findings are in agreement with an increased QTc duration found in LVNC patients carrying MIB1 mutations. These results provide insight into the outcomes of LVNC and relate its pathogenicity to impaired ventricular repolarization. PLoS One. 2025 May 7;20(5):e0314840. PLoS One 40334239 https://hdl.handle.net/20.500.12105/26842 Cardiac electrical abnormalities in a mouse model of left ventricular non-compaction cardiomyopathy.