Modulation of Presynaptic GABA Release by Oxidative Stress in Mechanically-isolated Rat Cerebral Cortical Neurons.
10.4196/kjpp.2010.14.3.127
- Author:
Eu Teum HAHM
1
;
Jung Woo SEO
;
Jinyoung HUR
;
Young Wuk CHO
Author Information
1. Department of Physiology, Biomedical Science Institute and Medical Research Center for Reactive Oxygen Species, Kyung Hee University School of Medicine, Seoul 130-701, Korea. ywcho@khu.ac.kr
- Publication Type:Original Article
- Keywords:
Gamma-aminobutyric acid;
Hydrogen peroxide;
Oxidative stress;
Inhibitory postsynaptic potentials
- MeSH:
Adenylyl Cyclases;
Aging;
Animals;
Catalase;
Cerebral Cortex;
Cyclic AMP-Dependent Protein Kinases;
Forskolin;
gamma-Aminobutyric Acid;
Hydrogen Peroxide;
Hydroxyl Radical;
Inhibitory Postsynaptic Potentials;
Membrane Potentials;
Neurons;
Oxidative Stress;
Parkinson Disease;
Presynaptic Terminals;
Rats;
Reactive Oxygen Species;
Superoxides;
Synaptic Transmission
- From:The Korean Journal of Physiology and Pharmacology
2010;14(3):127-132
- CountryRepublic of Korea
- Language:English
-
Abstract:
Reactive oxygen species (ROS), which include hydrogen peroxide (H2O2), the superoxide anion (O2-.), and the hydroxyl radical (OH.), are generated as by-products of oxidative metabolism in cells. The cerebral cortex has been found to be particularly vulnerable to production of ROS associated with conditions such as ischemia-reperfusion, Parkinson's disease, and aging. To investigate the effect of ROS on inhibitory GABAergic synaptic transmission, we examined the electrophysiological mechanisms of the modulatory effect of H2O2 on GABAergic miniature inhibitory postsynaptic current (mIPSCs) in mechanically isolated rat cerebral cortical neurons retaining intact synaptic boutons. The membrane potential was voltage-clamped at -60 mV and mIPSCs were recorded and analyzed. Superfusion of 1-mM H2O2 gradually potentiated mIPSCs. This potentiating effect of H2O2 was blocked by the pretreatment with either 10,000-unit/mL catalase or 300-micrometer N-acetyl-cysteine. The potentiating effect of H2O2 was occluded by an adenylate cyclase activator, forskolin, and was blocked by a protein kinase A inhibitor, N-(2-[p-bromocinnamylamino] ethyl)-5-isoquinolinesulfonamide hydrochloride. This study indicates that oxidative stress may potentiate presynaptic GABA release through the mechanism of cAMP-dependent protein kinase A (PKA)-dependent pathways, which may result in the inhibition of the cerebral cortex neuronal activity.
