Dopaminergic modulation of axonal potassium channels and action potential waveform in pyramidal neurons of prefrontal cortex. (9th May 2013)

• Record Type: Journal Article
• Authors: Yang, Jing; Ye, Mingyu; Tian, Cuiping; Yang, Mingpo; Wang, Yonghong; Shu, Yousheng
• Is Part Of: Journal of physiology. Volume 591:Number 13(2013:Jul.)
• Page Start: 3233
• Page End: 3251
• Publication Date: 2013-05-09
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/jphysiol.2013.251058
• Languages: English
• ISSNs: 0022-3751

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Key points</title> <p> <list id="l1" list-type="simple"> <list-item> <label> </label> <p>Dopamine and its receptors in prefrontal cortex (PFC) play an important role in regulating synaptic transmission and PFC‐mediated cognitive functions.</p> </list-item> <list-item> <label> </label> <p>Considering that presynaptic action potential waveform can modulate postsynaptic responses, we investigated whether axonal K<sup>+</sup> channels and action potential waveform are subjected to modulation by dopamine.</p> </list-item> <list-item> <label> </label> <p>Patch‐clamp recording from the axon of PFC pyramidal neurons showed that the activation of D1 and D2 dopamine receptors decreased and enhanced axonal K<sup>+</sup> currents, respectively. Further experiments revealed that intracellular cAMP–PKA pathway was involved in this dopaminergic modulation of axonal K<sup>+</sup> currents.</p> </list-item> <list-item> <label> </label> <p>Recording from axons disconnected from the soma revealed that the dopaminergic modulation still occurred, indicating the presence of functional dopamine receptors along the axon.</p> </list-item> <list-item> <label> </label> <p>We further demonstrate that axonal action potentials were substantially prolonged by D1 receptor activation. Taken together, our results reveal a new mechanism for dopaminergic modulation of neuronal signalling in PFC.</p> </list-item> </list> </p> <p> <bold>Abstract </bold> Voltage‐gated K<sup>+</sup> (K<sub>V</sub>) channels play critical roles in shaping neuronal signals. K<sub>V</sub> channels distributed in the perisomatic regions and thick dendrites of cortical pyramidal neurons have been extensively studied. However, the properties and regulation of K<sub>V</sub> 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<sup>+</sup> currents evoked by action potential (AP) waveform command (K<sub>AP</sub>) at the soma, whereas the rapidly activating but slowly inactivating K<sub>V</sub>1‐mediated D‐currents dominated the K<sub>AP</sub> at the axon. In addition, activation of D1‐like receptors for dopamine decreased the axonal K<sup>+</sup> 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<sup>+</sup> 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<sub>V</sub> 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<sub>V</sub> channels in regulating neuronal signalling.</p> </abstract>