Neurons are flexible electrophysiological entities in which the distribution and properties of ionic channels control their behaviors. Through simultaneous somatic and axonal whole-cell recording of layer 5 pyramidal cells, we demonstrate a remarkable differential expression of slowly inactivating K ؉ currents. Depolarizing the axon, but not the soma, rapidly activated a lowthreshold, slowly inactivating, outward current that was potently blocked by low doses of 4-aminopyridine, ␣-dendrotoxin, and rTityustoxin-K␣. Block of this slowly inactivating current caused a large increase in spike duration in the axon but only a small increase in the soma and could result in distal axons generating repetitive discharge in response to local current injection. Importantly, this current was also responsible for slow changes in the axonal spike duration that are observed after somatic membrane potential change. These data indicate that low-threshold, slowly inactivating K ؉ currents, containing Kv1.2 ␣ subunits, play a key role in the flexible properties of intracortical axons and may contribute significantly to intracortical processing.axon ͉ cortex ͉ plasticity ͉ synaptic transmission T he precise distribution and properties of ionic channels in cortical neurons strongly influence both the cell's intrinsic electrophysiological properties and its operation within cortical networks. Although the properties of cortical neuronal cell bodies and dendrites have been extensively studied, the study of neocortical axons has been largely confined to recordings from axonal segments near the cell body (e.g., see refs. 1 and 2).Far from being simple static structures that merely communicate spikes, the dynamical properties of intracortical axons may contribute critically to the operation of local cortical networks (reviewed in ref.3). Recently, it was shown that the amplitude of excitatory postsynaptic potentials evoked between excitatory neurons depends on the membrane potential of the presynaptic cell (4, 5). Modest somatic depolarization of presynaptic neocortical pyramidal cells increased the average excitatory postsynaptic potential (EPSP) amplitude evoked in nearby pyramidal cells. Interestingly, simultaneous axonal and somatic patch clamp recordings revealed that these somatic depolarizations increased axonal spike duration over a time course that was similar to the slow component of synaptic facilitation. These results suggest that information transmission within local cortical networks may operate in a mixed