Dopaminergic modulation of axonal potassium channels and action potential waveform in pyramidal neurons of prefrontal cortex

Voltage-gated K+ (K-V) channels play critical roles in shaping neuronal signals. K-V channels distributed in the perisomatic regions and thick dendrites of cortical pyramidal neurons have been extensively studied. However, the properties and regulation of K-V channels distributed in the thin axons remain unknown. In this study, by performing somatic and axonal patch-clamp recordings from layer 5 pyramidal neurons of prefrontal cortical slices, we showed that the rapidly inactivating A-currents mediated the transient K+ currents evoked by action potential (AP) waveform command (K-AP) at the soma, whereas the rapidly activating but slowly inactivating K(V)1-mediated D-currents dominated the K-AP at the axon. In addition, activation of D1-like receptors for dopamine decreased the axonal K+ currents, as a result of an increase in the activity of cAMP-PKA pathway. In contrast, activation of D2-like receptors showed an opposite effect on the axonal K+ currents. Further experiments demonstrated that functional D1-like receptors were expressed at the main axon trunk and their activation could broaden the waveforms of axonal APs. Together, these results show that axonal K-V channels were subjected to dopamine modulation, and this modulation could regulate the waveforms of propagating APs at the axon, suggesting an important role of dopaminergic modulation of axonal K-V channels in regulating neuronal signalling.