Abstract
This review article discusses mechanisms underlying impulse propagation in cardiac muscle with specific emphasis on the role of the cardiac cell-to-cell junction, called the “intercalated disc.”The first part of this review deals with the role of gap junction channels, formed by connexin proteins, as a determinant of impulse propagation. It is shown that, depending on the underlying structure of the cellular network, decreasing the conductance of gap junction channels (so-called “electrical uncoupling”) may either only slow, or additionally stabilize propagation and reverse unidirectional propagation block to bidirectional propagation. This is because the safety factor for propagation increases with decreasing intercellular electrical conductance. The role of heterogeneous connexin expression, which may be present in disease states, is also discussed. The hypothesis that so-called ephaptic impulse transmission plays a role in heart and can substitute for electrical coupling has been revived recently. Whereas ephaptic transmission can be demonstrated in theoretical simulations, direct experimental evidence has not yet been presented. The second part of this review deals with the interaction of three protein complexes at the intercalated disc: (1) desmosomal and adherens junction proteins, (2) ion channel proteins, and (3) gap junction channels consisting of connexins. Recent work has revealed multiple interactions between these three protein complexes which occur, at least in part, at the level of protein trafficking. Such interactions are likely to play an important role in the pathogenesis of arrhythmogenic cardiomyopathy, and may reveal new therapeutic concepts and targets.
Highlights
The observation that the heart is composed of billions of individual cardiac myocytes but functions as a highly coordinated syncytial structure has fascinated scientists since the nineteenth century (Engelmann, 1877)
Since impulse propagation was reduced by only 50% in tissue composed of the same cells, these observations raised the question of whether propagation of the cardiac impulse could occur in the absence of electrical cell-to-cell coupling
INTERACTIONS BETWEEN DESMOSOMAL PROTEINS, ION CHANNELS AND CONNEXINS AT THE INTERCALATED DISC In the previous paragraphs, this review has focused on the role of gap junctions in impulse transmission and propagation
Summary
This review article discusses mechanisms underlying impulse propagation in cardiac muscle with specific emphasis on the role of the cardiac cell-to-cell junction, called the “intercalated disc.”. The first part of this review deals with the role of gap junction channels, formed by connexin proteins, as a determinant of impulse propagation. It is shown that, depending on the underlying structure of the cellular network, decreasing the conductance of gap junction channels (so-called “electrical uncoupling”) may either only slow, or stabilize propagation and reverse unidirectional propagation block to bidirectional propagation. This is because the safety factor for propagation increases with decreasing intercellular electrical conductance.
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