biostudies-literatureAngelini MAmerican Heart AssociationKawata and Laubisch EndowmentsNHLBI NIH HHSNational Heart, Lung, and Blood InstituteKnut and Alice Wallenberg FoundationNational Institutes of HealthNIH HHSe202012584https://www.ebi.ac.uk/biostudies/studies/S-EPMC8552156biostudies-literatureUnknown153(12)Ventricular arrhythmias, a leading cause of sudden cardiac death, can be triggered by cardiomyocyte early afterdepolarizations (EADs). EADs can result from an abnormal late activation of L-type Ca2+ channels (LTCCs). Current LTCC blockers (class IV antiarrhythmics), while effective at suppressing EADs, block both early and late components of ICa,L, compromising inotropy. However, computational studies have recently demonstrated that selective reduction of late ICa,L (Ca2+ influx during late phases of the action potential) is sufficient to potently suppress EADs, suggesting that effective antiarrhythmic action can be achieved without blocking the early peak ICa,L, which is essential for proper excitation-contraction coupling. We tested this new strategy using a purine analogue, roscovitine,The Journal of general physiologySuppression of ventricular arrhythmias by targeting late L-type Ca2+ current.PMC8552156P01 HL078931R01 HL15229614SDG20300018R01 HL134346P01HL078931R01HL15229617POST336700461R01HL134346Olcese RAngelini MPezhouman ASavalli NOttolia MWeiss JNKaragueuzian HSScranton KSteccanella FCalmettes GChang MGPantazis AfalseSuppression of ventricular arrhythmias by targeting late L-type Ca2+ current.Ventricular arrhythmias, a leading cause of sudden cardiac death, can be triggered by cardiomyocyte early afterdepolarizations (EADs). EADs can result from an abnormal late activation of L-type Ca2+ channels (LTCCs). Current LTCC blockers (class IV antiarrhythmics), while effective at suppressing EADs, block both early and late components of ICa,L, compromising inotropy. However, computational studies have recently demonstrated that selective reduction of late ICa,L (Ca2+ influx during late phases of the action potential) is sufficient to potently suppress EADs, suggesting that effective antiarrhythmic action can be achieved without blocking the early peak ICa,L, which is essential for proper excitation-contraction coupling. We tested this new strategy using a purine analogue, roscovitine,2021-01-01T00:00:00Z2021 Dec2026-05-09T03:11:31.165Z2025-02-19T04:04:52.775ZS-EPMC85521563469880510.1085/jgp.202012584