Action Potential Initiation in a Damaged Axon Initial Segment

Abstract

We constructed a model for the initiation of the action potential (AP) in a damaged axon initial segment(AIS). We modelled the full axon including the AIS with a system of partial differential equations that we solved numerically. The damage was modelled on the AIS by having selected voltage-gated sodium channels affected by a coupled left-shift (CLS) of their activation and inactivation gating dynamics. We found that increased CLS lowered the threshold of spike initiation. We also found that CLS decreased the delay of spike initiation, especially for longer AIS. We also found that variability in the initiation timing increased with CLS. We also explored the effect of the geometry of the AIS on the initiation, finding that decreasing the radius favoured the initiation in the distal part of the AIS.