The GLP-1 Receptor Agonist Exendin-4 and Diazepam Differentially Regulate GABAA Receptor-Mediated Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons.
Glucagon-like peptide-1 (GLP-1) is a metabolic hormone that is secreted in a glucose-dependent manner and enhances insulin secretion. GLP-1 receptors are also found in the brain where their signalling affects neuronal activity. We have previously shown that the GLP-1 receptor agonists, GLP-1 and exendin-4 enhanced GABA-activated synaptic and tonic currents in rat hippocampal CA3 pyramidal neurons. The hippocampus is the centre for memory and learning and is important for cognition. Here we examined if exendin-4 similarly enhanced the GABA-activated currents in the presence of the benzodiazepine diazepam. In whole-cell recordings in rat brain slices, diazepam (1 μM), an allosteric positive modulator of GABAA receptors, alone enhanced the spontaneous inhibitory postsynaptic current (sIPSC) amplitude and frequency by a factor of 1.3 and 1.6, respectively, and doubled the tonic GABAA current normally recorded in the CA3 pyramidal cells. Importantly, in the presence of exendin-4 (10 nM) plus diazepam (1 μM), only the tonic but not the sIPSC currents transiently increased as compared to currents recorded in the presence of diazepam alone. The results suggest that exendin-4 potentiates a subpopulation of extrasynaptic GABAA receptors in the CA3 pyramidal neurons.
Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Sergiy V
SV
Korol
Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Zhe
Z
Jin
Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Bryndis
B
Birnir
D000818:Animals; D056654:CA3 Region, Hippocampal / Q000166:cytology* / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D004594:Electrophysiology; D000077270:Exenatide; D058785:GABA-A Receptor Agonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D055366:Synaptic Potentials / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology*
D058785:GABA-A Receptor Agonists; D010455:Peptides; D011963:Receptors, GABA-A; D014688:Venoms; D000077270:Exenatide; D003975:Diazepam