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

Abstract

Hydrogen sulfide (HS) 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 HS in the growth and maturation of neural networks however remains unclear. The aim of the present study is to reveal the effects of HS on neuronal spontaneous activity relevant to neuronal maturation in hippocampal slices of neonatal rats. Sodium hydrosulfide (NaHS) (100μM), a classical donor of HS 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 HS 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 HS 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 GABA-mediated currents. Finally, HS 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, HS prevents the enhanced neuronal excitability typical to early hippocampal networks.

Hydrogen sulfide alleviates cognitive deficiency and hepatic dysfunction in a mouse model of acute liver failure

“…In addition, H 2 S has been reported to induce a biphasic concentration-dependent effect (32). In the present study, it was observed that NaHS treatment (30 or 100 µmol/kg/day, intraperitoneal administration) manifested neuroprotective effects on TAA-treated mice, consistent with the previous study (33). Therefore, low and increased levels of H 2 S exhibited cytoprotective and cytotoxic effects, respectively (34).…”

Receptor Mechanisms Mediating the Pro-Nociceptive Action of Hydrogen Sulfide in Rat Trigeminal Neurons and Meningeal Afferents

“…The neuro-modulatory role of H 2 S was shown in the central and peripheral nervous system where it promotes the induction of long-term potentiation (LTP) in hippocampus (Abe and Kimura, 1996), inhibits giant depolarizing potentials in neonatal hippocampus (Yakovlev et al, 2017), affects NMDA-mediated currents (Abe and Kimura, 1996; Yakovlev et al, 2017), increases the transmitter release from motor nerve endings (Sitdikova et al, 2011; Gerasimova et al, 2013, 2015), or initiates contractile responses of the rat urinary bladder by stimulation of primary afferent neurons (Patacchini et al, 2004). …”

Effects of aminooxyacetic acid on hippocampal mitochondria in rats with chronic alcoholism: the analysis of learning and memory-related genes

“…In CBS-knockout mice, altering the activity of CBS has been shown to regulate the production of H2S (Eto et al, 2002). In addition, H2S participates in the pathophysiological processes of central nervous system-related diseases, such as epilepsy, stroke, neurodegenerative diseases, and neurotoxicity; its neuroprotective effects have been shown to depend heavily on its concentration and location (Yakovlev et al, 2017). AOAA has been shown to inhibit the expression of CBS, thereby reducing the formation of H2S, inhibiting Ca 2+ influx, and alleviating the intracellular Ca 2+ overload, which alleviates cell damage.…”