Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 189

as neutotransmitters released by the sympathetic and parasympathetic nerves reside
in the sarcolemma. Liganded receptors initiate signaling cascades to control the
activity of ion carriers. In addition, cardiomyocytes are connected by adhesion sites
and gap junctions that propogate electrochemical excitation waves.

5.2.1.1 Intercalated Discs

Cardiomyocytes are joined by regions of interdigitating sarcolemmas, the so-called
intercalated discs. They support intercellular communication necessary for proper
cardiac function.
These electromechanical junctions contain clusters of gap junctions to allow
electrochemical impulse, or action potential (APl), to spread rapidly and in a orderly
way so the cell contraction is almost synchronized. Cardiomyocytes then act as a
syncytium. Stimulation of an individual cell causes the contraction of the entire
myocardium.
Intercalated discs contain not only gap junctions for chemical communications,
but also mechanical junctions, composed of adherens junctions (fascia adherens)
with N-cadherin, catenins, and vinculin, as well as desmosomes that contain desmin,
desmoplakin, desmocollin, and desmoglein [ 333 ].
Adherens junctions and desmosomes dock terminal ends of the myofibrils,
intermediate filament network, and microtubules, thereby stabilizing the cyto-
skeleton and allowing a mechanical coupling between cardiomyocytes. Adherens
junctions especially anchor myofibrils and desmin cytoskeleton on cadherin mem-
brane sites. They occupy between-cell interdigitating regions transversely with
respect to the sarcomere. On the other hand, desmosomes and gap junctions are
located in membrane parts in the direction of the sarcomere axis.
At intercalated discs, zonula occludens protein ZO1 regulates the organization
of both gap and adherens junctions [ 334 ]. Zonula occludens protein ZO1 interacts
with Cadherin-2 (or N-cadherin); it regulates localization of gap junctions via its
association with the cadherin-2 complex.
At intercalated discs, Na V 1.5 and K V 1.5 channel subunits interact with junctional
proteic complexes ( intercalated disc interactome )[ 335 ]. Plakophilin-2, a desmoso-
mal molecule, influences gap junction-mediated coupling as well as Na V 1.5 channel
function. Cadherin-2 modulates gap junction and K V 1.5 functioning. Gap junction
protein connexin-43 interacts with the sodium channel complex component ankyrin-
G, which is required for proper intercellular adhesion and electrical coupling.
Connexin-43, which is needed for normal functioning of sodium and potassium
channels, regulates ankyrin-G transfer along microtubules into the intercalated disc
and conversely.