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PMID: 13679582 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Activation of ATP-sensitive K+ (K(ATP)) channels by H2O2 underlies glutamate-dependent inhibition of striatal dopamine release.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 20 ·2003-09-30 ·Pages 11729-34

Avshalumov MV, Rice ME

Abstract

In many cells, ATP-sensitive K+ channels (KATP channels) couple metabolic state to excitability. In pancreatic beta cells, for example, this coupling regulates insulin release. Although KATP channels are abundantly expressed in the brain, their physiological role and the factors that regulate them are poorly understood. One potential regulator is H2O2. We reported previously that dopamine (DA) release in the striatum is modulated by endogenous H2O2, generated downstream from glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor activation. Here we investigated whether H2O2-sensitive KATP channels contribute to DA-release modulation by glutamate and gamma-aminobutyric acid (GABA). This question is important because DA-glutamate interactions underlie brain functions, including motor control and cognition. Synaptic DA release was evoked by using local electrical stimulation in slices of guinea pig striatum and monitored in real time with carbon-fiber microelectrodes and fast-scan cyclic voltammetry. The KATP-channel antagonist glibenclamide abolished the H2O2-dependent increase in DA release usually seen with AMPA-receptor blockade by GYKI-52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] and the decrease in DA release seen with GABA-type-A-receptor blockade by picrotoxin. In contrast, 5-hydroxydecanoate, a mitochondrial KATP-channel blocker, was ineffective, as were sulpiride, a D2-receptor antagonist, and tertiapin, a G protein-coupled K+-channel inhibitor. Diazoxide, a sulfonylurea receptor 1 (SUR1)selective KATP-channel opener, prevented DA modulation by H2O2, glutamate, and GABA, whereas cromakalim, a SUR2-selective opener, did not. Thus, endogenous H2O2 activates SUR1-containing KATP channels in the plasma membrane to inhibit DA release. These data not only demonstrate that KATP channels can modulate CNS transmitter release in response to fast-synaptic transmission but also introduce H2O2 as a KATP-channel regulator.

MeSH Terms
Adenosine Triphosphate/metabolism Animals Corpus Striatum/drug effects,metabolism Dopamine/metabolism,pharmacology Guinea Pigs Hydrogen Peroxide/pharmacology In Vitro Techniques Male Mitochondria/drug effects,metabolism Potassium Channels/metabolism Receptors, Dopamine D2/metabolism
Chemicals
Potassium Channels Receptors, Dopamine D2 Adenosine Triphosphate Hydrogen Peroxide Dopamine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Avshalumov Marat V
Department of Physiology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Rice Margaret E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1834314100
Published
2003-09-30
Epub
2003-00-17
Pages
11729-34
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC208826
Subset
IM
Grants
NINDS NIH HHS · R01 NS036362 · United States
NINDS NIH HHS · R56 NS036362 · United States
NINDS NIH HHS · NS-36362 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1073/pnas.1834314100 PMC Full Text View journal details
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