Dynamic behavior of gap junctions in each cardiac cycle: a novel view on the electrical coupling of normal...

Two main mechanisms have been suggested for the propagation of action potentials in cardiac muscle cells: (1) the free flow of local circuit current through gap junctions and (2) the effect of electrical field. Different evidences confirm each of two mechanisms. We think that gap junctions are not continuously open in a normal heart cycle; instead, they open and close intermittently. In other words, gap junction has a dynamic behavior in each cardiac cycle, managing different routes of propagation in the diverse moments of normal cycle. Gap junctions could be open in phases 0, 1, 3, 4 and close in phase 2 (plateau) of action potential. Whenever gap junction is open, conduction can be fulfilled rapidly by current flow and whenever it is closed, the electrical field will be the main route of propagation. When the prejunctional cell is in the peak of action potential(AP), gap junction is closed and the postjunctional cell should use the electrical field to be stimulated. Then, when the prejunctional cell comes to the end of AP, the gap junction opens and current will potentiate the rising phase of AP in the postjunctional cell. Moreover, this process causes accumulation of calcium in the postjunctional cell near phase 2. We believe that our hypothesis on the mechanism of cardiac action potential propagation may have exciting advantages. This novel view on gap junction dynamic behavior may be useful for better exploitation of drugs or designing new remedies in arrhythmias. We also hypothesize that in conditions as cardiac failure, in which cardiac contractility is diminished and increasing intracellular calcium concentration is needed, gap junction closing drugs may be effective. It is worth noting that future clinical studies are needed to validate these predictions.