Dataset Information
Unraveling Impacts of Chamber-Specific Differences in Intercalated Disc Ultrastructure and Molecular Organization on Cardiac Conduction.
Ontology highlight
ABSTRACT: Background
Propagation of action potentials through the heart coordinates the heartbeat. Thus, intercalated discs, specialized cell-cell contact sites that provide electrical and mechanical coupling between cardiomyocytes, are an important target for study. Impaired propagation leads to arrhythmias in many pathologies, where intercalated disc remodeling is a common finding, hence the importance and urgency of understanding propagation dependence on intercalated disc structure. Conventional modeling approaches cannot predict changes in propagation elicited by perturbations that alter intercalated disc ultrastructure or molecular organization, because of lack of quantitative structural data at subcellular through nano scales.Objectives
This study sought to quantify intercalated disc structure at these spatial scales in the healthy adult mouse heart and relate them to chamber-specific properties of propagation as a precursor to understanding the effects of pathological intercalated disc remodeling.Methods
Using super-resolution light microscopy, electron microscopy, and computational image analysis, we provide here the first ever systematic, multiscale quantification of intercalated disc ultrastructure and molecular organization.Results
By incorporating these data into a rule-based model of cardiac tissue with realistic intercalated disc structure, and comparing model predictions of electrical propagation with experimental measures of conduction velocity, we reveal that atrial intercalated discs can support faster conduction than their ventricular counterparts, which is normally masked by interchamber differences in myocyte geometry. Further, we identify key ultrastructural and molecular organization features underpinning the ability of atrial intercalated discs to support faster conduction.Conclusions
These data provide the first stepping stone to elucidating chamber-specific effects of pathological intercalated disc remodeling, as occurs in many arrhythmic diseases.
SUBMITTER: Struckman HL
PROVIDER: S-EPMC11102000 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
Publications
Unraveling Impacts of Chamber-Specific Differences in Intercalated Disc Ultrastructure and Molecular Organization on Cardiac Conduction.
JACC. Clinical electrophysiology 20230726 12
<h4>Background</h4>Propagation of action potentials through the heart coordinates the heartbeat. Thus, intercalated discs, specialized cell-cell contact sites that provide electrical and mechanical coupling between cardiomyocytes, are an important target for study. Impaired propagation leads to arrhythmias in many pathologies, where intercalated disc remodeling is a common finding, hence the importance and urgency of understanding propagation dependence on intercalated disc structure. Convention ...[more]
