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 -