AMP kinase regulates K-ATP currents evoked by NMDA receptor stimulation in rat subthalamic nucleus neurons

Ke-Zhong Shen, V. Yakhnitsa, A. C. Munhall, Steven Johnson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Our lab recently showed that N-methyl-d-aspartate (NMDA) evokes ATP-sensitive K+ (K-ATP) currents in subthalamic nucleus (STN) neurons in slices of the rat brain. Both K-ATP channels and 5'-adenosine monophosphate-activated protein kinase (AMPK) are considered cellular energy sensors because their activities are influenced by the phosphorylation state of adenosine nucleotides. Moreover, AMPK has been shown to regulate K-ATP function in a variety of tissues including pancreas, cardiac myocytes, and hypothalamus. We used whole-cell patch clamp recordings to study the effect of AMPK activation on K-ATP channel function in STN neurons in slices of the rat brain. We found that bath or intracellular application of the AMPK activators A769662 and PT1 augmented tolbutamide-sensitive K-ATP currents evoked by NMDA receptor stimulation. The effect of AMPK activators was blocked by the AMPK inhibitor dorsomorphin (compound C), and by STO609, an inhibitor of the upstream AMPK activator CaMKKβ. AMPK augmentation of NMDA-induced K-ATP current was also blocked by intracellular BAPTA and by inhibitors of nitric oxide synthase and guanylyl cyclase. However, A769662 did not augment currents evoked by the K-ATP channel opener diazoxide. In the presence of NMDA, A769662 inhibited depolarizing plateau potentials and burst firing, both of which could be antagonized by tolbutamide or dorsomorphin. These studies show that AMPK augments NMDA-induced K-ATP currents by a Ca2+-dependent process that involves nitric oxide and cGMP. By augmenting K-ATP currents, AMPK activation would be expected to dampen the excitatory effect of glutamate-mediated transmission in the STN.

Original languageEnglish (US)
Pages (from-to)138-152
Number of pages15
JournalNeuroscience
Volume274
DOIs
StatePublished - Aug 22 2014

Fingerprint

Adenylate Kinase
Subthalamic Nucleus
Adenosine Monophosphate
Adenosine Triphosphate
Neurons
Protein Kinases
A 769662
Aspartic Acid
Tolbutamide
Calcium-Calmodulin-Dependent Protein Kinase Kinase
aspartic acid receptor
Diazoxide
Guanylate Cyclase
Brain
Protein Kinase Inhibitors
Baths
Cardiac Myocytes
Nitric Oxide Synthase
Adenosine
Hypothalamus

Keywords

  • AMP kinase
  • Brain slice
  • K-ATP
  • NMDA
  • Patch-clamp
  • Subthalamic nucleus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

AMP kinase regulates K-ATP currents evoked by NMDA receptor stimulation in rat subthalamic nucleus neurons. / Shen, Ke-Zhong; Yakhnitsa, V.; Munhall, A. C.; Johnson, Steven.

In: Neuroscience, Vol. 274, 22.08.2014, p. 138-152.

Research output: Contribution to journalArticle

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