Activity-mediated plasticity of GABA equilibrium potential in rat hippocampal CA1 neurons.
The equilibrium potential (E(GABA)(-PSC)) for gamma-aminobutyric acid (GABA) A receptor mediated inhibitory postsynaptic currents (PSCs) in hippocampal CA1 pyramidal neurons shifts when theta-burst stimulation (four pulses at 100 Hz in each burst in a train consisting of five bursts with an inter-burst interval of 200 ms, the train repeated thrice at 30-s intervals) is applied to the input. E(GABA)(-PSC) is regulated by K(+)/Cl(-) co-transporter (KCC2). GABA(B) receptors are implicated in modulating KCC2 levels. In the current study, the involvement of KCC2, as well as GABA(B) receptors, in theta-burst-mediated shifts in E(GABA)(-PSC) was examined. Whole-cell patch recordings were made from hippocampal CA1 pyramidal neurons (from 9 to 12 days old rats), in a slice preparation. Glutamatergic excitatory postsynaptic currents were blocked with dl-2-amino-5-phosphonovaleric acid (50 microM) and 6,7-dinitroquinoxaline-2,3-dione (20 microM). The PSC and the E(GABA)(-PSC) were stable when stimulated at 0.05 Hz. However, both changed following a 30-min stimulation at 0.5 or 1 Hz. Furosemide (500 microM) and KCC2 anti-sense in the recording pipette but not bumetanide (20 or 100 microM) or KCC2 sense, blocked the changes, suggesting KCC2 involvement. Theta-burst stimulation induced a negative shift in E(GABA)(-PSC), which was prevented by KCC2 anti-sense; however, KCC2 sense had no effect. CGP55845 (2 microM), a GABA(B) antagonist, applied in the superfusing medium, or GDP-beta-S in the recording pipette, blocked the shift in E(GABA)(-PSC). These results indicate that activity-mediated plasticity in E(GABA)(-PSC) occurs in hippocampal CA1 pyramidal neurons and theta-burst-induced negative shift in E(GABA)(-PSC) requires KCC2, GABA(B) receptors and G-protein activation.
Yang
B
B
Neuroscience Research Laboratory, Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
Tadavarty
R
R
Xu
J-Y
JY
Sastry
B R
BR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002034:Bumetanide / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D005665:Furosemide / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide; C085075:CGP 55845A; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005680:gamma-Aminobutyric Acid; D005665:Furosemide