Hydrogen sulfide inhibits giant depolarizing potentials and abolishes epileptiform activity of neonatal rat hippocampal slices

Aleksey V Yakovlev,Evgeniya D Kurmasheva,Rashid Giniatullin,Ilgam Khalilov,Guzel F Sitdikova

doi:10.1016/j.neuroscience.2016.10.051

Aleksey V Yakovlev, Evgeniya D Kurmasheva + Show 3 more

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https://doi.org/10.1016/j.neuroscience.2016.10.051

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Abstract

Hydrogen sulfide (H2S) is an endogenous gasotransmitter with neuroprotective properties that participates in the regulation of transmitter release and neuronal excitability in various brain structures. The role of H2S in the growth and maturation of neural networks however remains unclear. The aim of the present study is to reveal the effects of H2S on neuronal spontaneous activity relevant to neuronal maturation in hippocampal slices of neonatal rats. Sodium hydrosulfide (NaHS) (100μM), a classical donor of H2S produced a biphasic effect with initial activation and subsequent concentration-dependent suppression of network-driven giant depolarizing potentials (GDPs) and neuronal spiking activity. Likewise, the substrate of H2S synthesis l-cysteine (1mM) induced an initial increase followed by an inhibition of GDPs and spiking activity. Our experiments indicate that the increase in initial discharge activity by NaHS is evoked by neuronal depolarization which is partially mediated by a reduction of outward K+ currents. The subsequent decrease in the neuronal activity by H2S appears to be due to the rightward shift of activation and inactivation of voltage-gated Na+ currents, thus preventing network activity. NaHS also reduced N-methyl-d-aspartate (NMDA)-mediated currents, without essential effect on AMPA/kainate or GABAA-mediated currents. Finally, H2S abolished the interictal-like events induced by bicuculline. In summary, our results suggest that through the inhibitory action on voltage-gated Na+ channels and NMDA receptors, H2S prevents the enhanced neuronal excitability typical to early hippocampal networks.

Highlights

Hydrogen sulfide (H2S) has been recently identified as an important intra- and intercellular messenger, regulating various physiological and pathological processes (Kimura, 2010; Hermann et al, 2012a; Wang, 2012)
We first tested the actions of neonatal rats. Sodium hydrosulfide (NaHS) and the metabolic precursor of H2S, L-cysteine, on the extracellular recorded neuronal activity of immature hippocampus which is characterized by spontaneous network-driven giant depolarizing potentials (GDPs) (Ben-Ari et al, 1989), consisting mainly of GABAergic postsynaptic currents and bursts of multi-unit activity (MUA) (Fig. 1A)
All records were obtained from the CA3 region of the hippocampus which is centrally responsible in GDP generation (Khazipov et al, 1997)

Summary

Introduction

Hydrogen sulfide (H2S) has been recently identified as an important intra- and intercellular messenger, regulating various physiological and pathological processes (Kimura, 2010; Hermann et al, 2012a; Wang, 2012). In the central nervous system H2S induces long-term potentiation in the hippocampus (Abe and Kimura, 1996), modulates neuronal excitability of the subfornical organ, the nucleus of the solitary tract (Kuksis et al, 2014; Kuksis and Ferguson, 2015; Malik and Ferguson, 2016) and trigeminal neurons (Feng et al, 2013) and mediates central inhibition of the respiratory rhythm (Chen et al, 2013). H2S participates in the pathophysiology of central nervous system diseases such as epilepsy, stroke, neurodegenerative diseases and hyper-homocysteinemia (Wang, 2012; Luo et al, 2014). Neurotoxic or neuroprotective action of H2S is critically dependent on its concentration and cellular location (Wedmann et al, 2014)

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