Effects of persistent sodium current blockade in respiratory circuits depend on the pharmacological mechanism of action and network dynamics
Fig 6
A transient hyperpolarizing perturbation fails to elicit rebound bursting after simulated (A) TTX but not (B) RZ blockade of INaP.
(A & B) Top Panels: Vm- and hNaP-nullclines during baseline, hyperpolarization, and release from hyperpolarization. Arrows indicate the direction of the trajectory. (A & B) Bottom Panels: voltage trace of Vm during baseline hyperpolarization and release. Initial conditions that generate transient bursting trajectories are indicated by the filled red regions and only appear in the RZ case. For simulated TTX blockade in (A) gNaP = 1.25 nS. In this case, after hyperpolarization (middle panel), the equilibrium point (open circle) lies at an hNaP value that is too low to allow clearance of the left knee after release (right panel). For simulated RZ blockade in (B), Δh1/2 = −12 mV. Here, in the red region, and hence any hyperpolarization that allows the trajectory to enter the red region (e.g., center panel) will yield a burst upon release (right panel). For both simulations, gTonicE = 0.35 nS.