Objective The responsiveness of a neuron to external stimuli is likely to be regulated by the site of action potential initiation.Although initiation was axonal in many studies, somatic conductance can generate action potentials, suggesting that the soma contributes to spike initiation and may regulate firing.On the other hand, former studies mainly focused on the initiation of single spike, little is known about that of sequential spikes which are more significant in neuron encoding.This study is focusing on the generation of sequential spikes.Methods Simultaneous whole cell recordings from the soma and the axon were performed 9n cortical layer 5 pyramidal neurons of mice.Steady-state and cosinoidal waves were injected at soma and axon separately, then output spikes were recorded and spike frequency was computed.Activities of voltage dependent sodium channels on soma and axon were recorded in cell-attached mode.Results Steady-state depolarization had a more efficient input-output at soma compared to that at axon while cosinoidal waves induced more spikes at axon than that at soma.Further studies showed that, axonal Na+ channel availability was reduced during steady-state depolarization that made axonal spike frequency much lower than somatic one.Threshold currents and refractory periods, which are mediated by voltage-gated sodium channels, were lower at axon during short time depolarization but lower at soma during long time steady-state depolarization.Conclusion The dynamics of Na+ channels are different between soma and axon, which makes the initial site of spikes be variable according to the pattern of input signals.