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Role of A1 receptor-activated GIRK channels in the suppression of hippocampal seizure activity
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Hill, Emily, Hickman, Charlotte, Diez, Rebecca and Wall, Mark J. (2020) Role of A1 receptor-activated GIRK channels in the suppression of hippocampal seizure activity. Neuropharmacology, 164 . 107904. doi:10.1016/j.neuropharm.2019.107904
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WRAP-role-A1-receptor-activated-channels-suppression-seizure-activity-Hill-2019.pdf - Accepted Version - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (1819Kb) | Preview |
Official URL: http://doi.org/10.1016/j.neuropharm.2019.107904
Abstract
The neuromodulator adenosine is released during seizure activity to provide negative feedback suppression of on-going activity and to delay the occurrence of the next burst of activity. Adenosine acts via multiple G protein coupled receptors including the A1 receptor (A1R) which inhibits neurotransmitter release and hyperpolarises neuronal membrane potential. The hyperpolarisation is produced, at least in part, by the activation of G protein-activated inwardly rectifying K+ (GIRK) channels. We have used tertiapin-Q (TQ), a potent and selective inhibitor of GIRK channels, to assess the role of GIRK channels in controlling seizure activity in areas CA1 and CA2 of mouse hippocampal slices. TQ (100–300 nM) blocked ∼50% of the adenosine-mediated membrane potential hyperpolarisation of hippocampal CA1 and CA2 neurons. TQ (100 nM) had no significant effect on synaptic transmission in area CA1 of the hippocampus but enhanced transmission in CA2, an effect prevented by blocking A1Rs. TQ (100 nM) increased the frequency of spontaneous activity (induced by removing Mg2+ and increasing K+) and blunted the effects of exogenous adenosine on the suppression of activity. TQ had a significantly greater effect on electrically-stimulated seizure activity induced in CA2 versus that in CA1, producing a greater increase in both the duration and amplitude of the stimulated bursts. This is consistent with the greater A1R density and A1R activation tone in CA2. Thus GIRK channels play a role in the supressing effects of adenosine on seizure activity.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||||
| Library of Congress Subject Headings (LCSH): | Adenosine, Adenosine -- Receptors, Nervous system -- Degeneration -- Molecular aspects, Convulsions | ||||||||
| Journal or Publication Title: | Neuropharmacology | ||||||||
| Publisher: | Elsevier | ||||||||
| ISSN: | 0028-3908 | ||||||||
| Official Date: | 1 March 2020 | ||||||||
| Dates: |
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| Volume: | 164 | ||||||||
| Article Number: | 107904 | ||||||||
| DOI: | 10.1016/j.neuropharm.2019.107904 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||
| RIOXX Funder/Project Grant: |
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