Most studies consider voltage-gated ion channel biophysics as deterministic. However, individual ion channels undergo thermodynamic fluctuations which provoke stochastic transitions between closed and open states. This “channel-noise” leads to fluctuations of the membrane potential (Vm) and to unpredictability of the neuronal output. Channel noise has been mostly studied through somatic recordings which may underestimate it due to the great somatic capacitive load and the large somatic channels amount leading to an averaging of the individual channel stochasticity. Computational studies have suggested that thinner compartments such as axons are highly sensitive to channel noise but experimental evidence is lacking. By performing somatic, axonal and dendritic whole-cell recordings in cortical layer 5 pyramidal cells (L5PC), we observed larger channel noise in the axon and that this noise is partly due to Nav channels. Moreover, expression of Nav channels in an heterologous system (CHO cells) is enough to induce channel noise. Then, we found that introduction of channel noise in a multicompartimental model of L5PC induced a stronger spike jitter for desynchronized inputs. Finally, we found that this channel-noiseinduced spiking jitter provoked the filtering of inputs in function of their synchrony in a multi-layer neuronal network.