Figure 5. Fhf2KO strands are susceptible to conduction failure with reduction in gNaV and elevated temperatures.
(A) In Fhf2WT strand, a 78% reduction in sodium conductance leads to diminished action potential (AP) amplitude and slowed conduction velocity, but no block is observed. (B) In Fhf2KO strand, a 32% reduction in sodium conductance leads to progressive decay in AP amplitude, and conduction block. (C) [dV/dt]max for Fhf2WT and Fhf2KO strands plotted versus reductions in gNaV. For each strand, [dV/dt]max declines as gNaV decreases until point of failure. (D) Safety factor for Fhf2WT and Fhf2KO strands plotted versus reductions in gNaV. SF declines as gNaV decreases until point of failure. (E) Conduction velocity for Fhf2WT and Fhf2KO strands plotted versus reductions in gNaV. For each strand, CV declines as gNaV decreases until point of failure. (F) The Fhf2WT strand faithfully conducts action potentials when temperature is increased to 45°C. (G) The Fhf2KO strand fails to conduct at 41°C due to faster rates of open and closed state inactivation. (H) Conduction velocity for Fhf2WT and Fhf2KO strands plotted versus rising temperature. CV increases with temperature in the Fhf2WT strand, while decreasing in the Fhf2KO strand until failure temperature.