Axonal Action-Potential Initiation and Na+ Channel Densities in the Soma and Axon Initial Segment of Subicular Pyramidal Neurons

A long-standing hypothesis is that action potentials initiate first in the axon hillock/initial segment (AH–IS) region because of a locally high density of Na+ channels. We tested this idea in subicular pyramidal neurons by using patch-clamp recordings in hippocampal slices. Simultaneous recordings from the soma and IS confirmed that orthodromic action potentials initiated in the axon and then invaded the soma. However, blocking Na+ channels in the AH–IS with locally applied tetrodotoxin (TTX) did not raise the somatic threshold membrane potential for orthodromic spikes. TTX applied to the axon beyond the AH–IS (30–60 μm from the soma) raised the apparent somatic threshold by ∼8 mV. We estimated the Na+ current density in the AH–IS and somatic membranes by using cell-attached patch-clamp recordings and found similar magnitudes (3–4 pA/μm2). Thus, the present results suggest that orthodromic action potentials initiate in the axon beyond the AH–IS and that the minimum threshold for spike initiation of the neuron is not determined by a high density of Na+ channels in the AH–IS region.