title: Lithium acts as a potentiator of AMPAR currents in hippocampal CA1 cells by selectively increasing channel open probability.
abstract: Recent evidence suggests that lithium, which is used in the treatment of bipolar disorders, may act by influencing AMPAR properties at central glutamatergic synapses. While it is clear that lithium potentiates recombinant AMPAR responses in a subunit specific way, the origin of this potentiation is not known. We examined the effects of lithium on native AMPAR channels in CA1 pyramidal cells in hippocampal slices where AMPARs are expected to be associated with auxiliary subunits. We found that lithium produced a selective increase in single-channel open probability (P(open)), with little effect on single-channel conductance or burst length. From the present and previous finding it is likely that lithium causes a reduction in the time to recovery from desensitization, resulting in the observed increase in P(open). This would be consistent with the view that lithium acts like certain other allosteric AMPAR modulators to reduce the time spent in the desensitized state, but differs from those that act by slowing dissociation of glutamate.
authors.affiliation: Institute for Neurophysiology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Gebhardt
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Cull-Candy
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000502:physiology; D004594:Electrophysiology; D018698:Glutamic Acid / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D018021:Lithium Chloride / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D018698:Glutamic Acid; D018021:Lithium Chloride
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