Block of an ether-a-go-go-like K+ channel by imipramine rescues egl-2 excitation defects in Caenorhabditis elegans

David Weinshenker, Aguan Wei, Lawrence Salkoff, James H. Thomas

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

K+ channels are key regulators of cellular excitability. Mutations that activate K+ channels can lower cellular excitability, whereas those that inhibit K+ channels may increase excitability. We show that the Caenorhabditis elegans egl-2 gene encodes an eag K+ channel and that a gain- of-function mutation in egl-2 blocks excitation in neurons and muscles by causing the channel to open at inappropriately negative voltages. Tricyclic antidepressants reverse egl-2(gf) mutant phenotypes, suggesting that EGL-2 is a tricyclic target. We verified this by showing that EGL-2 currents are inhibited by imipramine. Similar inhibition is observed with the mouse homolog MEAG, suggesting that inhibition of EAG-like channels may mediate some clinical side effects of this class of antidepressants.

Original languageEnglish
Pages (from-to)9831-9840
Number of pages10
JournalJournal of Neuroscience
Volume19
Issue number22
DOIs
StatePublished - Nov 15 1999

Keywords

  • Antidepressant
  • Caenorhabditis elegans
  • Imipramine
  • K channel
  • Tricyclic
  • eag
  • egl-2

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