title: Hydrogen sulfide inhibits giant depolarizing potentials and abolishes epileptiform activity of neonatal rat hippocampal slices.
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.
authors.affiliation: Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia. Electronic address: alv.yakovlev@gmail.com.
authors.forename: Aleksey V
authors.initials: AV
authors.lastname: Yakovlev
authors.affiliation: Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia. Electronic address: harlequin18@gmail.com.
authors.forename: Evgeniya D
authors.initials: ED
authors.lastname: Kurmasheva
authors.affiliation: Cell Biology Laboratory, Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211, Neulaniementie 2, Kuopio, Finland. Electronic address: rashid.giniatullin@uef.fi.
authors.forename: Rashid
authors.initials: R
authors.lastname: Giniatullin
authors.affiliation: Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia; INMED-INSERM U901, 163, Avenue de Luminy, 13273 Marseille Cedex 09, France; Aix-Marseille University, 163, Avenue de Luminy, 13273 Marseille Cedex 09, France. Electronic address: ilgam.khalilov@inserm.fr.
authors.forename: Ilgam
authors.initials: I
authors.lastname: Khalilov
authors.affiliation: Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia. Electronic address: guzel.sitdikova@kpfu.ru.
authors.forename: Guzel F
authors.initials: GF
authors.lastname: Sitdikova
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000494:pharmacology*; D002414:Cations, Monovalent / Q000378:metabolism; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D046509:Tissue Culture Techniques
chemical_list: D000927:Anticonvulsants; D002414:Cations, Monovalent; D006862:Hydrogen Sulfide; D018696:Neuroprotective Agents; D011188:Potassium; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D012964:Sodium; D013779:Tetrodotoxin
keywords: NMDA-mediated currents; giant depolarizing potentials; hydrogen sulfide; interictal-like events; membrane potential; neonatal hippocampus