Figure 5.

In silico analysis identified ion channels and molecular processes that might contribute to inflammation-induced changes in action potential (AP) generation. We simulated the knockout (KO) and two-fold expression increase of three key model-identified ion channels (TRPA1, Piezo2, and Kv7.1) and the increase and decrease in the rates of four key model-identified key processes (GPCR phosphorylation, PKA inhibition, G_αq activation, and both Nav1.8 and Nav1.7 phosphorylation) using the nominal parameter set. The figure shows 5 s time courses of the membrane potential (V_m) before and after the addition of an inflammatory mediator, simulated using the nominal parameter set with all channels present (solid black line), with TRPA1 KO (red line), and with the G_αq subunit activation rate reduced by 10-fold in response to mechanical forces of (A) 10 mN, (B) 20 mN, and (C) 40 mN. In the top panels of (A–C), which depict the AP response before addition of an inflammatory mediator, the black line representing the V_m changes in the nominal model (no modifications) overlaps the green line representing the effect of G_αq activation reduction. The table shows the magnitude of AP fold change values for every modification performed using the nominal parameter set.