Cell Junctions in the Specialized Conduction System of the Heart

Abstract

Anchoring cell junctions are integral in maintaining electro-mechanical coupling of ventricular ‘working’ cardiomyocytes; however, their role in cardiomyocytes of the cardiac conduction system (CCS) remains less clear. Recent studies in genetic mouse models and humans highlight the appearance of these cell junctions alongside gap junctions in the CCS and also show that defects in these structures and their components are associated with conduction impairments in the CCS. Here we outline current evidence supporting an integral relationship between anchoring and gap junctions in the CCS. Specifically we focus on (1) molecular and ultrastructural evidence for cell-cell junctions in specialized cardiomyocytes of the CCS, (2) genetic mouse models specifically targeting cell-cell junction components in the heart which exhibit CCS conduction defects and (3) human clinical studies from patients with cell-cell junction-based diseases that exhibit CCS electrophysiological defects.

Striatins as plaque molecules of zonulae adhaerentes in simple epithelia, of tessellate junctions in stratified epithelia, of cardiac composite junctions and of various size classes of lateral adherens junctions in cultures of epithelia- and carcinoma-derived cells

“…Colocalization of striatin with other CJ molecules has also been found in a significant proportion of the junctions of the Purkinje network of conducting cells (Fig. 7 c-c’’; for an extensive recent review of cardiac conduction cells, see Mezzano et al 2014 ). In addition, we have noted, in the conductive cells, a few striatin-positive junctional reaction sites that are negative for all desmosome-specific marker proteins and other junctions that are desmoplakin- and plakophilin-2-positive but negative for all striatin antibodies tested (not shown).…”

DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere assembly

“…In controls, the membranes of adjoining myocytes were closely opposed and formed a discrete line (arrows, Figure 2I) flanked by electron-dense areas containing the adherens junctions, desmosomes, and gap junctions of these specialized adhesion sites (Delmar and McKenna, 2010; Mezzano et al, 2014; Vite and Radice, 2014). In contrast, lower-density material was frequently observed between the membranes of adjacent cardiomyocytes in the hearts of Daam1/2 DKO mice (arrows, Figure 2J).…”

Effects of different doses of 2,3‐dimercaptosuccinic acid‐modified Fe2O3nanoparticles on intercalated discs in engineered cardiac tissues

“…Besides the electrochemical coupling of cardiac cells in ECTs, mechanical junctions including adherens junctions and desmosomes are two other functional elements in regulation of cell communication …”

“…Besides the electrochemical coupling of cardiac cells in ECTs, mechanical junctions including adherens junctions and desmosomes are two other functional elements in regulation of cell communication. 28,29 We firstly determined the effects of DMSA-IRONs on adherens junctions of cardiac cells in ECTs. The expression of N-cadherin indicated the formation of adherens junctions.…”