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 mu m from the soma) raised the apparent somatic threshold by similar to 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/mu m(2)). 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.