Key result
Adding many gap-junction channels (1,000 to 10,000 per junction) in a cardiac muscle model inhibited transverse propagation, which could only be overcome by greatly increasing the longitudinal resistance of the interstitial fluid.
Why the study?
Does the addition of gap-junction channels inhibit transverse propagation of action potentials in a cardiac muscle model?
Does the addition of gap-junction channels inhibit transverse propagation of action potentials in a cardiac muscle model?
Computational modeling demonstrates that strong longitudinal coupling via gap junctions can paradoxically inhibit transverse propagation of action potentials, providing insights into potential mechanisms of reentrant arrhythmias.
Model findings suggest gap junctions may paradoxically impair transverse conduction; hypothesis-generating for reentry mechanisms, not ready for clinical translation.
The effect of adding many gap-junctions (g-j) channels between contiguous cells in a linear chain on transverse propagation between parallel chains was examined in a 5 x 5 model (5 parallel chains of 5 cells each) for cardiac muscle. The action potential upstrokes were simulated using the PSpice program for circuit analysis. Either a single cell was stimulated (cell A1) or the entire chain was stimulated simultaneously (A-chain). Transverse velocity was calculated from the total propagation time (TPT) from when the first AP crossed a Vm of -20 mV and the last AP crossed -20 mV. The number of g-j channels per junction was varied from zero to 100, 1,000 and 10,000 (Rgj of infinity, 100 MOmega, 10 MOmega, 1.0 MOmega, respectively). The longitudinal resistance of the interstitial fluid (ISF) space between the parallel chains (Rol2) was varied between 200 KOmega (standard value) and 1.0, 5.0, and 10 MOmega. The higher the Rol2 value, the tighter the packing of the chains. It was found that adding many g-j channels inhibited transverse propagation by blocking activation of all 5 chains, unless Rol2 was greatly increased above the standard value of 200 KOmega. This was true for either method of stimulation. This was explained by, when there is strong longitudinal coupling between all 5 cells of a chain awaiting excitation, there must be more transfer energy (i.e., more current) to simultaneously excite all 5 cells of a chain.
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Sperelakis et al. (2005) studied Cardiac muscle transverse propagation (simulation). Addition of gap-junction channels vs. Zero gap-junction channels was evaluated on Transverse propagation (number of chains responding and total propagation time). Adding many gap-junction channels (1,000 to 10,000 per junction) in a cardiac muscle model inhibited transverse propagation, which could only be overcome by greatly increasing the longitudinal resistance of the interstitial fluid.
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