Mechanisms of cardiac conduction: a history of revisions

Abstract

Cardiac conduction is the process by which electrical excitation spreads through the heart, triggering individual myocytes to contract in synchrony. Defects in conduction disrupt synchronous activation and are associated with life-threatening arrhythmias in many pathologies. Therefore, it is scarcely surprising that this phenomenon continues to be the subject of active scientific inquiry. Here we provide a brief review of how the conceptual understanding of conduction has evolved over the last century and highlight recent, potentially paradigm-shifting developments.

Keywords: cardiac conduction; ephaptic coupling; gap junctions; modeling; myocardium.

Fig. 1.

Schematic cartoon illustrating the mechanism of ephaptic coupling. A: sodium channels (shown in red) on the depolarized (green) myocyte's membrane activate and withdraw sodium ions (Na⁺) from the restricted extracellular cleft at the intercalated disk. As a result, the transmembrane potential (V_m,1) of the first myocyte is elevated. B: concomitant depletion of positive charge from the extracellular cleft lowers the local extracellular potential (Φ_e). This leads to an increase in the second, resting (red) myocyte's transmembrane potential (V_m,2), defined as the difference between its intracellular potential and the extracellular potential (Φ_e). In turn, sodium channels located at or near the intercalated disk of the second myocyte activate. C: sodium enters the second myocyte via these channels further depolarizing it and triggering an action potential. Thus activation is communicated ephaptically from cell to cell without the direct transfer of ions between them.