Fig. 8.
Depolarization block in response to a current step. A: small current step from a hyperpolarized holding potential leads to pacing (A1), but a large step leads to block (A2). B: NaV current was replaced with a virtual NaV current from the model in C but without slow inactivation. Normal pacing (B1) but abnormal depolarization block results (B2). [A and B adapted from Qian et al. (2014).] C: simulations using the model of Qian et al. (2014) with a holding current of −0.25 μA/cm2 and steps to 0 in C1 and 0.375 in C2. The leak and K+ conductances were increased by a factor of 5 and the NaV conductance by 4.5 to produce abrupt failure of APs. Moreover, the n activation variable was unyoked from the h inactivation variable. D: available, noninactivated fraction of NaV channels recovers sufficiently between APs during pacing (D1) but not upon entry to block (D2).