Intercellular Electrical Communication in the Heart: A New, Active Role for the Intercalated Disk

Abstract

Cardiac conduction is the propagation of electrical excitation through the heart and is responsible for triggering individual myocytes to contract in synchrony. Canonically, this process has been thought to occur electrotonically, by means of direct flow of ions from cell to cell. The intercalated disk (ID), the site of contact between adjacent myocytes, has been viewed as a structure composed of mechanical junctions that stabilize the apposition of cell membranes and gap junctions which constitute low resistance pathways between cells. However, emerging evidence suggests a more active role for structures within the ID in mediating intercellular electrical communication by means of non-canonical ephaptic mechanisms. This review will discuss the role of the ID in the context of the canonical, electrotonic view of conduction and highlight new, emerging possibilities of its playing a more active role in ephaptic coupling between cardiac myocytes.

The Living Scar – Cardiac Fibroblasts and the Injured Heart

“…In cardiac myocytes, this region contains elevated levels of Cx43 and the sodium channel protein Na v 1.5. Combined with narrow inter-membrane volumes at these sites, these proteins can create the potential for cell-to-cell transmission of electrical activation at the perinexus via an electric field-based mechanism (ephaptic coupling) [107, 108]. …”

Mutations in cardiovascular connexin genes

“…Increasing attention has been recently given to the ‘gap junction proteome’, the ‘connexin interactome’ or the ‘connexome’, a protein interacting network with the Cx as central mediator (Laird, ; Fowler et al., ; Agullo‐Pascual et al., ). The cardiac intercalated disc, for example, appears to host such an interacting complex of gap junctions, desmosomes and sodium channels that together control electrical coupling, intercellular adhesion and excitability (Agullo‐Pascual et al., ; Veeraraghavan et al., ). Maintenance of hemichannel and/or gap junction functionality and integrity is essential to conserve cell‐to‐cell communication and thus homeostasis in a wide range of tissues.…”

Cardiomyocyte maturation: It takes a village to raise a kid

“…CM attach to one another through specialized portions of the membrane termed intercalated discs [5]. Intercalated discs contain a large number of gap junctions that facilitate the passage of ions between cardiomyocytes, which is essential for propagation of the action potential [9]. Excitation-Contraction Coupling (ECC) refers to the mechanism through which the cardiac action potential initiates contraction of the cardiomyocyte [10].…”

“…Excitation-Contraction Coupling (ECC) refers to the mechanism through which the cardiac action potential initiates contraction of the cardiomyocyte [10]. Membrane depolarization induces a large influx of calcium ions, resulting in an intracellular spike of calcium that initiates the coordinated shortening of the actin-myosin fibrils to produce the CM contraction [9]. The rapid depolarization of the membrane potential is transduced to the interior of the cell through T-tubules, which release calcium ions stored within the sarcoplasmic reticulum [11].…”

“…T-tubule networks result from invaginations of the sarcolemma that occur at the Z line at the end of each sarcomere and serve to ensure that the entire cell depolarizes rapidly and homogenously [11]. CM modulate their contractile output in response to a wide variety of stimuli by altering ion currents, calcium handling and myofilament properties [9]. …”