Figure 4. Computational models of Fhf2^WT and Fhf2^KO cardiomyocyte strands.

(A) Strand model designed to include 111 cells, each measuring 100 microns aligned end-to-end, connected by gap junctions (Gj = 772.8 nS at 37°C). (B) Simulation of action potential (AP) propagation through strand. 0.5msec current injection into the first cell results in AP propagation through entire Fhf2^WT strand. The AP propagates with conduction velocity (CV) = 0.475 mm/msec. (C) Similar injection of current into the Fhf2^KO strand results in slowed AP propagation (CV = 0.339 mm/msec) with decreased AP amplitude in all cells. (D) Sodium current influx in cell 50 as a function of time. Sodium current influx is reduced in the Fhf2^KO strand, despite the same density of sodium conductance (gNa_V). (E) In cell 15 of the Fhf2^WT strand, sodium channel availability is approximately 50% at resting potential with peak Na_V activation peaking much earlier than Na_V inactivation. (F) In cell 15 of the Fhf2^KO strand, reduced sodium current is the consequence of approximately 74% Na_V steady-state inactivation at the resting potential, further Na_V closed state inactivation during the voltage rise preceding peak Na_V activation, and faster decay of the current due to faster Na_V open state inactivation.