Ephaptic coupling and the source-sink effect of cardiac conduction

As a result of the electrotonic effect, under gap junction coupling, a critical number of excited cells is needed to elicit electrical conduction in cardiac tissue, a phenomenon called the source-sink effect. However, it is unclear how ephaptic coupling affects the source-sink effect. To address this issue, we carry out computer simulations to investigate the effects of ephaptic coupling and its interaction with gap junction coupling on conduction triggered by the following types of depolarization: (i) an external stimulation; (ii) a delayed afterdepolarization; and (iii) automaticity. Simulations were carried out using a one-dimensional cable with the presence of a cleft between two adjacent myocytes and junctional ion channel distributions. We show that: (i) under pure ephaptic coupling, only one stimulated cell is needed to elicit conduction, implying that there is no source-sink effect; (i) the minimum number of stimulated (or delayed afterdepolarization or oscillatory) cells needed to elicit a conduction increases as gap junction conductance increases, as predicted by the gap junction coupling theory; and (iii) the dependence of the source-sink effect on the cleft width exhibits complex behaviours, which are mainly caused by self-attenuation of the junctional sodium current as a result of the ephaptic effect and self-enhancement of the junctional inward rectifier potassium current as a result of an increase of potassium concentration in the cleft. In conclusion, ephaptic coupling and cleft width play non-trivial roles in the source-sink effect of cardiac conduction and thus may be non-trivial for arrhythmogenesis under disease conditions in which gap junctions and cleft structure are altered. KEY POINTS: Gap junction coupling is recognized as the primary mechanism of cardiac conduction, but ephaptic coupling may also play a non-trivial role. Source-sink effects are a key feature of cardiac conduction, and it is unclear how they are affected by ephaptic coupling. Computer simulations are used to investigate how source-sink effects are altered by ephaptic coupling and its interaction with gap junction coupling. Under pure ephaptic coupling, only one stimulated cell is needed to elicit conduction, implying that there is no source-sink effect. The minimum number of depolarized cells needed to elicit a conduction exhibits complex behaviours and depends on the manner of depolarization. These effects are mainly caused by self-attenuation of the junctional sodium current as a result of the ephaptic effect and self-enhancement of the inward rectifier potassium current as a result of increase of potassium concentration in the cleft.