Lithium acts as a potentiator of AMPAR currents in hippocampal CA1 cells by selectively increasing channel open probability.
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.
Gebhardt
Christine
C
Institute for Neurophysiology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Cull-Candy
Stuart G
SG
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*
D018091:Receptors, AMPA; D018698:Glutamic Acid; D018021:Lithium Chloride
Eur J Neurosci. 1998 Jul;10(7):2433-43
9749771
Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):10064-7
16785437
J Physiol. 1995 Jan 15;482 ( Pt 2):325-52
7536248
J Cell Biol. 2003 May 26;161(4):805-16
12771129
J Neurosci. 2004 Jul 21;24(29):6578-89
15269270
Neuron. 1994 Nov;13(5):1195-203
7946356
J Neurophysiol. 1999 Apr;81(4):1506-12
10200187
Nature. 2006 Mar 23;440(7083):456-62
16554805
Nature. 2005 Jun 23;435(7045):1052-8
15858532
Biophys J. 2007 Apr 1;92(7):2392-402
17208968
Ann N Y Acad Sci. 2003 Nov;1003:273-91
14684452
Ann N Y Acad Sci. 2003 Nov;1003:250-72
14684451
Epilepsy Res. 2006 Jun;69(3):273-94
16621450
J Neurosci. 2000 Jan 1;20(1):89-102
10627585
Mol Pharmacol. 2003 Aug;64(2):269-78
12869631
Brain Res. 1986 Jun 11;375(2):302-12
3015332
Biochem Pharmacol. 2006 Apr 28;71(9):1273-88
16442080
J Neurosci Res. 2003 Sep 15;73(6):865-9
12949913
J Neurosci. 1997 Jun 15;17(12):4672-87
9169528
Science. 1990 Aug 3;249(4968):556-60
2166337
J Neurosci. 1996 Mar 15;16(6):1982-9
8604042
Nat Neurosci. 2003 Aug;6(8):803-10
12872125
J Physiol. 2006 Jun 1;573(Pt 2):371-94
16527860
Curr Drug Targets CNS Neurol Disord. 2004 Jun;3(3):181-94
15180479
Neuroscience. 1997 May;78(2):385-91
9145795
Neuron. 1998 Oct;21(4):907-18
9808475
Neurosci Lett. 1999 Dec 31;277(3):153-6
10626836
J Physiol. 1990 Mar;422:203-25
1972190
News Physiol Sci. 2000 Apr;15:83-89
11390884
J Neurosci. 2005 Mar 9;25(10):2682-6
15758178