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

• DOI: 10.1073/pnas.0403683101
• Publication Date: 2004-06-25T00:25:50Z
• Authors: E. Palma; D. A. Ragozzino; S. Di Angelantonio; G. Spinelli; F. Trettel; A. Martinez-Torres; G. Torchia; A. Arcella; G. Di Gennaro; P. P. Quarato; V. Esposito; G. Cantore; R. Miledi; F. Eusebi
• Keywords: Neocortex; GABAA-rho receptor; Gamma-Aminobutyric Acid

The properties of γ-aminobutyric acid (GABA) type A receptors (GABA receptors) microtransplanted from the human epileptic brain to plasma membrane Xenopus oocytes were compared with those recorded directly neurons, or glial cells, in brains slices. Cell membranes isolated specimens, surgically obtained six patients afflicted drug-resistant temporal lobe epilepsy (TLE) injected into frog oocytes. Within a few hours, these acquired GABA that generated currents an unusual run-down, which was inhibited by orthovanadate and okadaic acid. In contrast, derived nonepileptic hippocampal uncus, mouse brain, recombinant rat α1β2γ2-GABA exhibited much less pronounced GABA-current run-down. Moreover, pyramidal neurons neocortex slices same stronger run-down than neurons. Interestingly, neighboring cells remained substantially stable after repetitive activation. Therefore, excessive observed membrane-injected recapitulates essentially what occurs rather cells. Quantitative RT-PCR analyses TLE specimens revealed -receptor β1, β2, β3, γ2 subunit mRNAs significantly overexpressed (8- 33-fold) control autopsy tissues. Our results suggest abnormal GABA-receptor transcription leads expression run-down-enhanced receptors. Blockage phosphatases stabilizes strengthens GABAergic inhibition. It may be this process can targeted develop new treatments for intractable epilepsy.