We describe here a general technique for the graded inhibition of cellular
excitability in vivo. Inhibition is accomplished by expressing a geneticall
y modified Shaker K+ channel (termed the EKO channel) in targeted cells. Un
like native K+ channels, the EKO channel strongly shunts depolarizing curre
nt: activating at potentials near E-K and not inactivating. Selective targe
ting of the channel to neurons, muscles, and photoreceptors in Drosophila u
sing the Gal4-UAS system results in physiological and behavioral effects co
nsistent with attenuated excitability in the targeted cells, often with los
s of neuronal function at higher transgene dosages. By permitting the incre
mental reduction of electrical activity, the EKO technique can be used to a
ddress a wide range of questions regarding neuronal function.