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

J Physiol. 2013 Jul 1;591(13):3233-51. doi: 10.1113/jphysiol.2013.251058. Epub 2013 Apr 8.

Abstract

Voltage-gated K(+) (KV) channels play critical roles in shaping neuronal signals. KV channels distributed in the perisomatic regions and thick dendrites of cortical pyramidal neurons have been extensively studied. However, the properties and regulation of KV 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 (KAP) at the soma, whereas the rapidly activating but slowly inactivating KV1-mediated D-currents dominated the KAP 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 KV 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 KV channels in regulating neuronal signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Axons / physiology*
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dopamine / physiology*
  • In Vitro Techniques
  • Potassium Channels, Voltage-Gated / physiology*
  • Prefrontal Cortex / physiology*
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / physiology
  • Receptors, Dopamine D2 / physiology

Substances

  • Potassium Channels, Voltage-Gated
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Dopamine