Figure 8. Role of Na⁺ accumulation in the rate dependence of the AP.

The myocyte was paced as previously [38] with a stepwise reduction in BCL, and corresponding AP characteristics were defined for each BCL. (A) Shortening of the BCL increases both the subsarcolemmal and cytosolic [Na⁺], especially at BCLs 400 ms and 300 ms. (B) The values of APD₃₀ calculated from simulations are compared to those reported by Dawodu et al. [38], and Neef et al. [70]. (C) The steep dependence of APD₉₀ on the BCL reported by Dawodu et al. [38], Bosch et al. [72] and Dobrev & Ravens [73] is reproduced by the model. (D) Continued fast pacing starting from a quiescent steady-state results in a dramatic accumulation of intracellular Na⁺. (E) APD adaptation in control situation conditions and [Na⁺]_i “clamped” to the quiescent steady-state value. (F) AP shape at BCLs 1600, 800 and 400 ms after 5 minutes of pacing starting from a quiescent steady-state. (G) Accumulation of Na⁺ due to fast pacing, continued for 5 minutes, increases Na⁺/K⁺-ATPase current (I _NKA) substantially.