Pfizer COVID-19 vaccine appointments are available to our patients. Sign up for Connect today to schedule your vaccination. Continue your routine care with us by scheduling an in-person appointment or Video Visit.

The Purkinje-myocardial junction is the anatomical origin of ventricular arrhythmia in CPVT.

TitleThe Purkinje-myocardial junction is the anatomical origin of ventricular arrhythmia in CPVT.
Publication TypeJournal Article
Year of Publication2022
AuthorsBlackwell DJ, Faggioni M, Wleklinski MJ, Gomez-Hurtado N, Venkataraman R, Gibbs CE, Baudenbacher FJ, Gong S, Fishman GI, Boyle PM, Pfeifer K, Knollmann BC
JournalJCI Insight
Date Published2022 Jan 06

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmia syndrome due to gene mutations that render RYR2 calcium release channels hyperactive, causing spontaneous calcium release and delayed afterdepolarizations (DADs). What remains unknown is the cellular source of ventricular arrhythmia triggered by DADs - Purkinje cells in the conduction system or ventricular cardiomyocytes in the working myocardium. To answer this question, we used a genetic approach in mice to knock out cardiac calsequestrin either in Purkinje cells or in ventricular cardiomyocytes. Total loss of calsequestrin in the heart causes a severe CPVT phenotype in mice and humans. We found that loss of calsequestrin only in ventricular myocytes produced a full-blown CPVT phenotype, whereas mice with loss of calsequestrin only in Purkinje cells were comparable to wild-type mice. Subendocardial chemical ablation or restoration of calsequestrin expression in subendocardial cardiomyocytes neighboring Purkinje cells was sufficient to protect against catecholamine-induced arrhythmias. In silico modeling demonstrated that DADs in ventricular myocardium can trigger full action potentials in the Purkinje fiber, but not vice versa. Hence, ectopic beats in CPVT are likely generated at the Purkinje-myocardial junction via a heretofore unrecognized tissue mechanism, whereby DADs in the ventricular myocardium trigger full action potentials in adjacent Purkinje cells.

Alternate JournalJCI Insight
PubMed ID34990403