Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain

Proceedings of the National Academy of Sciences of the United States of America
Eleonora PalmaFabrizio Eusebi

Abstract

The properties of gamma-aminobutyric acid (GABA) type A receptors (GABA(A) receptors) microtransplanted from the human epileptic brain to the plasma membrane of Xenopus oocytes were compared with those recorded directly from neurons, or glial cells, in human brains slices. Cell membranes isolated from brain specimens, surgically obtained from six patients afflicted with drug-resistant temporal lobe epilepsy (TLE) were injected into frog oocytes. Within a few hours, these oocytes acquired GABA(A) receptors that generated GABA currents with an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, receptors derived from membranes of a nonepileptic hippocampal uncus, membranes from mouse brain, or recombinant rat alpha 1 beta 2 gamma 2-GABA receptors exhibited a much less pronounced GABA-current run-down. Moreover, the GABA(A) receptors of pyramidal neurons in temporal neocortex slices from the same six epileptic patients exhibited a stronger run-down than the receptors of rat pyramidal neurons. Interestingly, the GABA(A) receptors of neighboring glial cells remained substantially stable after repetitive activation. Therefore, the excessive GABA-current run-down observed in the membrane-injected oocy...Continue Reading

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Citations

Sep 24, 2005·Anatomy and Embryology·A GorjiE-J Speckmann
Sep 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cristina RosetiFabrizio Eusebi
Sep 2, 2009·Proceedings of the National Academy of Sciences of the United States of America·Cristina RosetiFabrizio Eusebi
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Manuela MazzuferiMichele Simonato
Jun 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Agenor LimonRicardo Miledi
Oct 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·D RagozzinoF Eusebi
Jan 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·E PalmaF Eusebi
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jacques J LaschetRené Pumain
Dec 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Eleonora PalmaFabrizio Eusebi
Feb 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·Eleonora PalmaFabrizio Eusebi
May 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·E PalmaF Eusebi
Jul 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Agenor LimonRicardo Miledi
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Oct 21, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Antonio GambardellaEleonora Palma
Jan 26, 2020·International Journal of Molecular Sciences·Pierangelo CifelliEleonora Palma
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Sep 17, 2013·Epilepsia·Cristina RosetiEleonora Palma
May 17, 2021·Cell Death & Disease·Carlo BrighiSilvia Di Angelantonio
May 3, 2019·Neuroscience·Cristina RosetiEleonora Palma

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