PMID- 10559392
OWN - NLM
STAT- MEDLINE
DCOM- 19991202
LR  - 20191023
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 22
DP  - 1999 Nov 15
TI  - Block of an ether-a-go-go-like K(+) channel by imipramine rescues egl-2
      excitation defects in Caenorhabditis elegans.
PG  - 9831-40
AB  - 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.
FAU - Weinshenker, D
AU  - Weinshenker D
AD  - Department of Genetics, University of Washington, Seattle, Washington 98195, USA.
FAU - Wei, A
AU  - Wei A
FAU - Salkoff, L
AU  - Salkoff L
FAU - Thomas, J H
AU  - Thomas JH
LA  - eng
GR  - R01NS24785/NS/NINDS NIH HHS/United States
GR  - R01NS30187/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for
      Neuroscience
JID - 8102140
RN  - 0 (Ether-A-Go-Go Potassium Channels)
RN  - 0 (Helminth Proteins)
RN  - 0 (Kcnh1 protein, mouse)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Potassium Channels)
RN  - 9H154DI0UP (Ethyl Methanesulfonate)
RN  - OGG85SX4E4 (Imipramine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Caenorhabditis elegans/genetics/*physiology
MH  - Chemotaxis
MH  - Ether-A-Go-Go Potassium Channels
MH  - Ethyl Methanesulfonate
MH  - Female
MH  - Genotype
MH  - Helminth Proteins/genetics
MH  - Imipramine/*pharmacology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Motor Activity
MH  - Mutagenesis
MH  - Neurons/*physiology
MH  - Oviposition
MH  - Phenotype
MH  - Potassium Channel Blockers
MH  - Potassium Channels/chemistry/*physiology
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
PMC - PMC6782970
EDAT- 1999/11/13 00:00
MHDA- 1999/11/13 00:01
CRDT- 1999/11/13 00:00
PHST- 1999/11/13 00:00 [pubmed]
PHST- 1999/11/13 00:01 [medline]
PHST- 1999/11/13 00:00 [entrez]
PST - ppublish
SO  - J Neurosci. 1999 Nov 15;19(22):9831-40.