TY - JOUR

T1 - The intercalated disc

T2 - a unique organelle for electromechanical synchrony in cardiomyocytes

AU - Nielsen, Morten S.

AU - van Opbergen, Chantal J.M.

AU - van Veen, Toon A.B.

AU - Delmar, Mario

PY - 2023

Y1 - 2023

N2 - The intercalated disc (ID) is a highly specialized structure that connects cardiomyocytes via mechanical and electrical junctions. Although described in some detail by light microscopy in the 19th century, it was in 1966 that electron microscopy images showed that the ID represented apposing cell borders and provided detailed insight into the complex ID nanostructure. Since then, much has been learned about the ID and its molecular composition, and it has become evident that a large number of proteins, not all of them involved in direct cell-to-cell coupling via mechanical or gap junctions, reside at the ID. Furthermore, an increasing number of functional interactions between ID components are emerging, leading to the concept that the ID is not the sum of isolated molecular silos but an interacting molecular complex, an "organelle" where components work in concert to bring about electrical and mechanical synchrony. The aim of the present review is to give a short historical account of the ID's discovery and an updated overview of its composition and organization, followed by a discussion of the physiological implications of the ID architecture and the local intermolecular interactions. The latter will focus on both the importance of normal conduction of cardiac action potentials as well as the impact on the pathophysiology of arrhythmias.

AB - The intercalated disc (ID) is a highly specialized structure that connects cardiomyocytes via mechanical and electrical junctions. Although described in some detail by light microscopy in the 19th century, it was in 1966 that electron microscopy images showed that the ID represented apposing cell borders and provided detailed insight into the complex ID nanostructure. Since then, much has been learned about the ID and its molecular composition, and it has become evident that a large number of proteins, not all of them involved in direct cell-to-cell coupling via mechanical or gap junctions, reside at the ID. Furthermore, an increasing number of functional interactions between ID components are emerging, leading to the concept that the ID is not the sum of isolated molecular silos but an interacting molecular complex, an "organelle" where components work in concert to bring about electrical and mechanical synchrony. The aim of the present review is to give a short historical account of the ID's discovery and an updated overview of its composition and organization, followed by a discussion of the physiological implications of the ID architecture and the local intermolecular interactions. The latter will focus on both the importance of normal conduction of cardiac action potentials as well as the impact on the pathophysiology of arrhythmias.

KW - arrhythmia

KW - cardiac physiology

KW - cell adhesion

KW - gap junction

KW - intercalated disc

UR - http://www.scopus.com/inward/record.url?scp=85159740702&partnerID=8YFLogxK

U2 - 10.1152/physrev.00021.2022

DO - 10.1152/physrev.00021.2022

M3 - Review

C2 - 36731030

AN - SCOPUS:85159740702

VL - 103

SP - 2271

EP - 2319

JO - Physiological Reviews

JF - Physiological Reviews

SN - 0031-9333

IS - 3

ER -