Block of an Ether-a-go-go-like K(+) Channel by Imipramine Rescues Egl-2 Excitation Defects in Caenorhabditis Elegans

Overview

Journal J Neurosci

Specialty Neurology

Date 1999 Nov 13

PMID 10559392

Citations 31

Authors

D Weinshenker

A Wei

L Salkoff

J H Thomas

Affiliations

Soon will be listed here.

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.

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