Targeted attenuation of electrical activity in Drosophila using a genetically modified K(+) channel

Neuron. 2001 Sep 13;31(5):699-711. doi: 10.1016/s0896-6273(01)00415-9.

Abstract

We describe here a general technique for the graded inhibition of cellular excitability in vivo. Inhibition is accomplished by expressing a genetically modified Shaker K(+) channel (termed the EKO channel) in targeted cells. Unlike native K(+) channels, the EKO channel strongly shunts depolarizing current: activating at potentials near E(K) and not inactivating. Selective targeting of the channel to neurons, muscles, and photoreceptors in Drosophila using the Gal4-UAS system results in physiological and behavioral effects consistent with attenuated excitability in the targeted cells, often with loss of neuronal function at higher transgene dosages. By permitting the incremental reduction of electrical activity, the EKO technique can be used to address a wide range of questions regarding neuronal function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological / genetics
  • Animals
  • Behavior, Animal / physiology
  • Cells, Cultured
  • Drosophila Proteins
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Female
  • Gene Dosage
  • Gene Expression Regulation, Developmental / genetics
  • Gene Targeting*
  • Genes, Lethal / physiology
  • Larva / genetics
  • Larva / growth & development
  • Larva / metabolism
  • Membrane Potentials / genetics*
  • Muscles / embryology
  • Muscles / metabolism
  • Muscles / physiopathology
  • Mutation / physiology
  • Nervous System / cytology
  • Nervous System / embryology
  • Nervous System / metabolism*
  • Neural Inhibition / genetics
  • Neurons / cytology
  • Neurons / metabolism*
  • Neurons, Afferent / cytology
  • Neurons, Afferent / metabolism
  • Phenotype
  • Photoreceptor Cells, Invertebrate / cytology
  • Photoreceptor Cells, Invertebrate / metabolism
  • Potassium Channels / genetics*
  • Potassium Channels / metabolism
  • Shaker Superfamily of Potassium Channels
  • Synaptic Transmission / genetics
  • Transgenes / physiology

Substances

  • Drosophila Proteins
  • Potassium Channels
  • Sh protein, Drosophila
  • Shaker Superfamily of Potassium Channels