title: Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus: possible implications for epilepsy.
abstract: Acid-sensing ion channels (ASICs) play an important role in numerous functions in the central and peripheral nervous systems ranging from memory and emotions to pain. The data correspond to a recent notion that each neuron and many glial cells of the mammalian brain express at least one member of the ASIC family. However, the mechanisms underlying the involvement of ASICs in neuronal activity are poorly understood. However, there are two exceptions, namely, the straightforward role of ASICs in proton-based synaptic transmission in certain brain areas and the role of the Ca(2+)-permeable ASIC1a subtype in ischaemic cell death. Using a novel orthosteric ASIC antagonist, we have found that ASICs specifically control the frequency of spontaneous inhibitory synaptic activity in the hippocampus. Inhibition of ASICs leads to a strong increase in the frequency of spontaneous inhibitory postsynaptic currents. This effect is presynaptic because it is fully reproducible in single synaptic boutons attached to isolated hippocampal neurons. In concert with this observation, inhibition of the ASIC current diminishes epileptic discharges in a low Mg(2+) model of epilepsy in hippocampal slices and significantly reduces kainate-induced discharges in the hippocampus in vivo Our results reveal a significant novel role for ASICs.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'.
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine.
authors.forename: O
authors.identifier: 0000-0002-5499-4245
authors.initials: O
authors.lastname: Ievglevskyi
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine.
authors.forename: D
authors.identifier: 0000-0002-4126-2563
authors.initials: D
authors.lastname: Isaev
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine.
authors.forename: O
authors.identifier: 0000-0001-6869-7834
authors.initials: O
authors.lastname: Netsyk
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine.
authors.forename: A
authors.identifier: 0000-0002-2871-5548
authors.initials: A
authors.lastname: Romanov
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine.
authors.forename: M
authors.identifier: 0000-0003-0278-8519
authors.initials: M
authors.lastname: Fedoriuk
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine.
authors.forename: O
authors.identifier: 0000-0003-3288-4974
authors.initials: O
authors.lastname: Maximyuk
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine.
authors.forename: E
authors.identifier: 0000-0002-2969-7847
authors.initials: E
authors.lastname: Isaeva
authors.affiliation: Research Division for Clinical Pharmacology, Medical Corporation, JyuryoGroup, Kumamoto Kinoh Hospital, 6-8-1 Yamamuro, Kitaku, Kumamoto 860-8518, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Akaike
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine krishtal@biph.kiev.ua.
authors.forename: O
authors.identifier: 0000-0003-3342-9930
authors.initials: O
authors.lastname: Krishtal
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000494:pharmacology*; D062565:Acid Sensing Ion Channels / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004827:Epilepsy / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D009415:Nerve Net / Q000378:metabolism; D051381:Rats
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels
keywords: acid-sensing ion channels; epilepsy; hippocampus; presynaptic modulation