Targeted attenuation of electrical activity in Drosophila using a genetically modified K(+) channel.
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.
White
B H
BH
Department of Pharmacology, Yale University School of Medicine, P.O. Box 208066, New Haven, CT 06520, USA. benjamin.white@yale.edu
Osterwalder
T P
TP
Yoon
K S
KS
Joiner
W J
WJ
Whim
M D
MD
Kaczmarek
L K
LK
Keshishian
H
H
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002478:Cells, Cultured; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018390:Gene Targeting; D005804:Genes, Lethal / Q000502:physiology; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008564:Membrane Potentials / Q000235:genetics*; D009132:Muscles / Q000196:embryology / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000502:physiology; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D009433:Neural Inhibition / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels; D009435:Synaptic Transmission / Q000235:genetics; D019076:Transgenes / Q000502:physiology
D029721:Drosophila Proteins; D015221:Potassium Channels; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels