Differential actions of AMP kinase on ATP-sensitive K+ currents in ventral tegmental area and substantia nigra zona compacta neurons

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

ATP-sensitive K+ (K-ATP) channels play significant roles in regulating the excitability of dopamine neurons in the substantia nigra zona compacta (SNC). We showed previously that K-ATP channel function is up-regulated by AMP-activated protein kinase (AMPK). This study extended these studies to the neurons adjacent to the SNC in the ventral tegmental area (VTA). Using patch pipettes to record whole-cell currents in slices of rat midbrain, we found that the AMPK activator A769662 increased the amplitude of currents evoked by the K-ATP channel opener diazoxide in presumed dopamine-containing VTA neurons. However, current evoked by diazoxide with A769662 was significantly smaller in VTA neurons compared to SNC neurons. Moreover, a significantly lower proportion of VTA neurons responded to diazoxide with outward current. However, A769662 was able to increase the incidence of diazoxide-responsive neurons in the VTA. In contrast, A769662 did not potentiate diazoxide-evoked currents in presumed non-dopamine VTA neurons. These results show that AMPK activation augments K-ATP currents in presumed dopamine neurons in the VTA and SNC, although diazoxide-evoked currents remain less robust in the VTA. We conclude that K-ATP channels may play important physiological roles in VTA and SNC dopamine neurons.

Original languageEnglish (US)
JournalEuropean Journal of Neuroscience
DOIs
StateAccepted/In press - 2017

Fingerprint

Adenylate Kinase
Ventral Tegmental Area
Herpes Zoster
Diazoxide
A 769662
Adenosine Triphosphate
Neurons
AMP-Activated Protein Kinases
Dopaminergic Neurons
Pars Compacta
Mesencephalon
Dopamine

Keywords

  • AMP kinase
  • ATP-sensitive potassium channel
  • Diazoxide
  • Dopamine neuron
  • Patch-clamp recording

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{1f6bb5adefa943dfa6b71ba2bae46b07,
title = "Differential actions of AMP kinase on ATP-sensitive K+ currents in ventral tegmental area and substantia nigra zona compacta neurons",
abstract = "ATP-sensitive K+ (K-ATP) channels play significant roles in regulating the excitability of dopamine neurons in the substantia nigra zona compacta (SNC). We showed previously that K-ATP channel function is up-regulated by AMP-activated protein kinase (AMPK). This study extended these studies to the neurons adjacent to the SNC in the ventral tegmental area (VTA). Using patch pipettes to record whole-cell currents in slices of rat midbrain, we found that the AMPK activator A769662 increased the amplitude of currents evoked by the K-ATP channel opener diazoxide in presumed dopamine-containing VTA neurons. However, current evoked by diazoxide with A769662 was significantly smaller in VTA neurons compared to SNC neurons. Moreover, a significantly lower proportion of VTA neurons responded to diazoxide with outward current. However, A769662 was able to increase the incidence of diazoxide-responsive neurons in the VTA. In contrast, A769662 did not potentiate diazoxide-evoked currents in presumed non-dopamine VTA neurons. These results show that AMPK activation augments K-ATP currents in presumed dopamine neurons in the VTA and SNC, although diazoxide-evoked currents remain less robust in the VTA. We conclude that K-ATP channels may play important physiological roles in VTA and SNC dopamine neurons.",
keywords = "AMP kinase, ATP-sensitive potassium channel, Diazoxide, Dopamine neuron, Patch-clamp recording",
author = "Wu, {Yan Na} and Ke-Zhong Shen and Steven Johnson",
year = "2017",
doi = "10.1111/ejn.13756",
language = "English (US)",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Differential actions of AMP kinase on ATP-sensitive K+ currents in ventral tegmental area and substantia nigra zona compacta neurons

AU - Wu, Yan Na

AU - Shen, Ke-Zhong

AU - Johnson, Steven

PY - 2017

Y1 - 2017

N2 - ATP-sensitive K+ (K-ATP) channels play significant roles in regulating the excitability of dopamine neurons in the substantia nigra zona compacta (SNC). We showed previously that K-ATP channel function is up-regulated by AMP-activated protein kinase (AMPK). This study extended these studies to the neurons adjacent to the SNC in the ventral tegmental area (VTA). Using patch pipettes to record whole-cell currents in slices of rat midbrain, we found that the AMPK activator A769662 increased the amplitude of currents evoked by the K-ATP channel opener diazoxide in presumed dopamine-containing VTA neurons. However, current evoked by diazoxide with A769662 was significantly smaller in VTA neurons compared to SNC neurons. Moreover, a significantly lower proportion of VTA neurons responded to diazoxide with outward current. However, A769662 was able to increase the incidence of diazoxide-responsive neurons in the VTA. In contrast, A769662 did not potentiate diazoxide-evoked currents in presumed non-dopamine VTA neurons. These results show that AMPK activation augments K-ATP currents in presumed dopamine neurons in the VTA and SNC, although diazoxide-evoked currents remain less robust in the VTA. We conclude that K-ATP channels may play important physiological roles in VTA and SNC dopamine neurons.

AB - ATP-sensitive K+ (K-ATP) channels play significant roles in regulating the excitability of dopamine neurons in the substantia nigra zona compacta (SNC). We showed previously that K-ATP channel function is up-regulated by AMP-activated protein kinase (AMPK). This study extended these studies to the neurons adjacent to the SNC in the ventral tegmental area (VTA). Using patch pipettes to record whole-cell currents in slices of rat midbrain, we found that the AMPK activator A769662 increased the amplitude of currents evoked by the K-ATP channel opener diazoxide in presumed dopamine-containing VTA neurons. However, current evoked by diazoxide with A769662 was significantly smaller in VTA neurons compared to SNC neurons. Moreover, a significantly lower proportion of VTA neurons responded to diazoxide with outward current. However, A769662 was able to increase the incidence of diazoxide-responsive neurons in the VTA. In contrast, A769662 did not potentiate diazoxide-evoked currents in presumed non-dopamine VTA neurons. These results show that AMPK activation augments K-ATP currents in presumed dopamine neurons in the VTA and SNC, although diazoxide-evoked currents remain less robust in the VTA. We conclude that K-ATP channels may play important physiological roles in VTA and SNC dopamine neurons.

KW - AMP kinase

KW - ATP-sensitive potassium channel

KW - Diazoxide

KW - Dopamine neuron

KW - Patch-clamp recording

UR - http://www.scopus.com/inward/record.url?scp=85032925048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032925048&partnerID=8YFLogxK

U2 - 10.1111/ejn.13756

DO - 10.1111/ejn.13756

M3 - Article

C2 - 29057540

AN - SCOPUS:85032925048

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

ER -