N-ethylmaleimide blocks depolarization-induced suppression of inhibition and enhances GABA release in the rat hippocampal slice in vitro

Wade Morishita, Sergei A Kirov, Thomas A. Pitler, Laura A. Martin, Robert A. Lenz, Bradley E. Alger

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Regulation of synaptic, GABA(A) receptor-mediated inhibition is a process of critical importance to normal brain function. Recently, we have described a phenomenon in hippocampus of a transient, yet marked, decrease in spontaneous, GABA(A) receptor-mediated IPSCs after depolarization activated Ca2+ influx into a pyramidal cell. This process, depolarization-induced suppression of inhibition (DSI), is absent in hippocampal cells that previously had been exposed to pertussis toxin in vivo, implicating a G- protein in the DSI process. To circumvent the problem that a single cell cannot be studied before and after G-protein block using the pertussis toxin pretreatment method, we have used the sulfhydryl alkylating agent N- ethylmaleimide (NEM), which blocks pertussis toxin-sensitive G-proteins, to determine whether acute inhibition of G-proteins can eliminate DSI of spontaneous IPBCs (sIPSCs). In whole-cell recordings from CA1 pyramidal cells that were first determined to express DSI, we have found that NEM does block DSI of sIPSCs. We also report that DSI of monosynaptic, evoked IPSCs is blocked by NEM, suggesting that a similar mechanism underlies both forms of DSI. It was of interest that DSI was abolished at a time when NEM had increased, not decreased, GABA transmission. Indeed, NEM greatly increased quantal GABA release by a Ca2+-independent mechanism, an observation with potentially important implications for understanding synaptic GABA release.

Original languageEnglish (US)
Pages (from-to)941-950
Number of pages10
JournalJournal of Neuroscience
Volume17
Issue number3
Publication statusPublished - Feb 1 1997
Externally publishedYes

    Fingerprint

Keywords

  • GABA
  • hippocampus
  • IPSC
  • mIPSCs
  • NEM
  • transmitter release

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this