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KCI등재 학술저널

Modulation of Presynaptic GABA Release by Oxidative Stress in Mechanically-isolated Rat Cerebral Cortical Neurons

Modulation of Presynaptic GABA Release by Oxidative Stress in Mechanically-isolated Rat Cerebral Cortical Neurons

Reactive oxygen species (ROS), which include hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), the superoxide anion (O<sub>2</sub><sup>&#8722;</sup>·), 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 H<sub>2</sub>O<sub>2</sub> 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 &#8722;60 mV and mIPSCs were recorded and analyzed. Superfusion of 1-mM H<sub>2</sub>O<sub>2</sub> gradually potentiated mIPSCs. This potentiating effect of H<sub>2</sub>O<sub>2</sub> was blocked by the pretreatment with either 10,000-unit/mL catalase or 300-&#1356;M N-acetyl-cysteine. The potentiating effect of H<sub>2</sub>O<sub>2</sub> 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.

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