This study looks at the effect on spike initiation of a genetic mutation that specifically impacts an AIS-specific protein (beta-IV spectrin). That mutation seems to affect the density of Nav channels at the AIS, which becomes close to the somatic density (with the caveat that this observation is based on immunochemistry, and it is not so obvious to precisely compare the axonal and somatic fluorescence signals quantitatively). Electrophysiologically, the consequences are: higher threshold, lower onset rapidness, lower spiking precision, poorer high-frequency tracking properties.

The authors insist on the fact that the results show that a high density of Nav channels is not necessary for axonal initiation of spikes. Indeed the mutant cells generally show a biphasic phase plot characteristic of axonal initiation. They found the same thing in a biophysical model (from Hallermann et al. 2012), where Nav density is modified to be the same in AIS and soma. This, however, is not particularly surprising since Nav channels have a lower activation voltage in the AIS than in the soma (both in the model and in empirical observations). The authors cite an old paper (Moore 1983) that proposes another potential reason why spikes initiate in the axon, which is interesting: if the soma and AIS have the same Nav channel density, spikes would still initiate in the AIS because less current leaks in the direction of the axon than towards the dendrite (both resistance and capacitance). This, however, is only true if there are no dendritic Nav channels, but the model used here actually has the same Nav density in the soma and dendrites, so the reason why spikes initiate in the AIS in this case is because of lower activation voltage of axonal channels.