Macroscopic current properties of experimental and simulated WT and Y1795C channels. Shown in each panel is a summary of experimentally determined records (left) and simulated current (right). In the experimental records, open circles are WT (n = 8) and filled circles are Y1795C (n = 9) channels. Theoretical symbols overlap except in c (where the thick line represents Y1795C channels in the right panel). (a) Shown is the voltage dependence of inactivation following 500-millisecond conditioning pulses. Normalized current is plotted versus conditioning pulse voltage. (b) The Y1795C mutation does not affect the voltage dependence of activation (see Methods). (c) The Y1795C mutation increases peak experimentally determined (left) and computed current (right). Experimental currents were measured in lowered extracellular Na⁺ to ensure voltage control. In the simulation, the slowing of the transition rate from open to inactivation states acts to increase open-state probability in the Y1795C mutant compared with WT, resulting in an increase in macroscopic I_Na. WT macroscopic I_Na is about 20% and 15% less than Y1795C I_Na in the experiment and the simulation, respectively. Note that simulated density is larger because it is computed in a simulated cardiac myocyte in full Na⁺ solutions. μA, microAmps; μF, microfarad.