title: Changes of K+ -Cl- cotransporter 2 (KCC2) and circuit activity in propofol-induced impairment of long-term potentiation in rat hippocampal slices.
abstract: Enhancing inhibition via gamma-aminobutyric acid type A (GABA(A)) receptors contributes to anesthetic-induced impairment of long-term potentiation (LTP) of excitatory synaptic transmission, which may account for general anesthesia-associated memory impairment (amnesia). The neuron-specific K+ -Cl- cotransporter 2 (KCC2) is necessary for fast synaptic inhibition via maintaining the low intracellular chloride concentration required for the hyperpolarizing actions of GABA via GABA(A) receptors. To explore a possible role of KCC2-dependent inhibition in anesthetic-induced impairment of LTP, we used field excitatory postsynaptic potentials (fEPSP) recording and immunoblotting to study the effect of propofol on LTP maintenance and KCC2 expression in CA1 region of rat hippocampal slices. We found that propofol (30 microM) not only impaired LTP expression but also prevented LTP-accompanied downregulation of KCC2 without affecting the basal transmission of glutamatergic synapses. Moreover, the recurrent inhibition in hippocampal slices was enhanced by propofol. These propofol-induced effects were completely abolished by picrotoxin, a specific GABA(A) receptor-chloride channel blocker. Thus, enhancement of GABAergic inhibition and suppression of neuronal excitability may account for the sustained expression of KCC2 and the impairment of LTP by propofol. Together, this study supports a novel role for KCC2 in LTP expression and gives hints to a molecular mechanism, by which anesthetics might cause impairment of LTP.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Neng
authors.initials: N
authors.lastname: Gong
authors.forename: Tian-Le
authors.initials: TL
authors.lastname: Xu
mesh_terms: D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D010852:Picrotoxin / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D018686:Anesthetics, Intravenous; D018756:GABA Antagonists; D010852:Picrotoxin; D015742:Propofol; D027981:Symporters; D000096922:K Cl- Cotransporters