Carbenoxolone impairs LTP and blocks NMDA receptors in murine hippocampus.
Effects of the gap junction blocker carbenoxolone (CBX) on tetanus- and taurine-induced long-term potentiation (LTP) were studied on Schaffer collateral-CA1 field excitatory postsynaptic potentials (fEPSPs) in mouse hippocampal slices. Preincubation with 10 microM CBX reduced the amount of LTP induced by weak theta-burst stimulation (TBS) or a single train of stimuli (HFS; 1s at 100 Hz), but did not affect LTP induced by 30-min perfusion with 10 mM taurine. Incubation with 50-100 microM CBX 15 min before HFS or TBS abolished tetanus-induced LTP. At 100 microM CBX, the concentration that is used for the blockade of gap junctions in vitro, a long-lasting depression of fEPSPs was observed which persisted under the blockade of NMDA receptors, and receptors for corticosteroids. A similar depression was produced by the CBX inactive analogue glycyrrhizic acid and the broad spectrum calcium channel antagonist ruthenium red. Whole-cell patch-clamp recordings from acutely isolated CA1 pyramidal neurons showed that CBX exerts a selective dose-dependent inhibition of NMDA-evoked currents with an IC(50)=104 microM. Thus the widely used gap junction uncoupler CBX acts as an antagonist at NMDA receptors and consequently impairs the induction of LTP.
Department of Neurophysiology, Heinrich-Heine-University, D-40001 Düsseldorf, Germany.
Aisa N
AN
Chepkova
Olga A
OA
Sergeeva
Helmut L
HL
Haas
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013148:Spironolactone / Q000494:pharmacology; D013654:Taurine / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D006727:Hormone Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D013654:Taurine; D013148:Spironolactone; D015735:Mifepristone; D002229:Carbenoxolone