title: Regulation of GABA Equilibrium Potential by mGluRs in Rat Hippocampal CA1 Neurons.
abstract: The equilibrium potential for GABA-A receptor mediated currents (EGABA) in neonatal central neurons is set at a relatively depolarized level, which is suggested to be caused by a low expression of K+/Cl- co-transporter (KCC2) but a relatively high expression of Na+-K+-Cl- cotransporter (NKCC1). Theta-burst stimulation (TBS) in stratum radiatum induces a negative shift in EGABA in juvenile hippocampal CA1 pyramidal neurons. In the current study, the effects of TBS on EGABA in neonatal and juvenile hippocampal CA1 neurons and the underlying mechanisms were examined. Metabotropic glutamate receptors (mGluRs) are suggested to modulate KCC2 and NKCC1 levels in cortical neurons. Therefore, the involvement of mGluRs in the regulation of KCC2 or NKCC1 activity, and thus EGABA, following TBS was also investigated. Whole-cell patch recordings were made from Wistar rat hippocampal CA1 pyramidal neurons, in a slice preparation. In neonates, TBS induces a positive shift in EGABA, which was prevented by NKCC1 antisense but not NKCC1 sense mRNA. (RS)-a-Methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, blocked TBS-induced shifts in both juvenile and neonatal hippocampal neurons. While blockade of mGluR1 or mGluR5 alone could interfere with TBS-induced shifts in EGABA in neonates, only a combined blockade could do the same in juveniles. These results indicate that TBS induces a negative shift in EGABA in juvenile hippocampal neurons but a positive shift in neonatal hippocampal neurons via corresponding changes in KCC2 and NKCC1 expressions, respectively. mGluR activation seems to be necessary for both shifts to occur while the specific receptor subtype involved seems to vary.
authors.affiliation: Neuroscience Research Laboratory, Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
authors.forename: Padmesh S
authors.initials: PS
authors.lastname: Rajput
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
authors.forename: Ujendra
authors.initials: U
authors.lastname: Kumar
authors.affiliation: Neuroscience Research Laboratory, Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
authors.forename: Bhagavatula R
authors.initials: BR
authors.lastname: Sastry
mesh_terms: D000200:Action Potentials; D000818:Animals; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D008297:Male; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D011963:Receptors, GABA-A; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D005680:gamma-Aminobutyric Acid