DNA MOLECULES ENCODING CTENOCEPHALIDES FELIS GLUTAMATE GATED CHLORIDE CHANNELS

摘要

To date, L-glutamate-gated chloride (GluC1) channels have been observed onlyin invertebrate organisms. Modulators of this channel (either agonists orantagonists) will interfere with neurotransmission. For example, agents suchas avermectins activate the GluCl, causing paralysis due to blocking ofneurotransmitter release, resulting in death of the organism. Because GluClchannels are invertebrate specific, they are excellent targets for thediscovery of novel insecticides, anthelminths and parasiticides that willdisplay a marked safety profile because of the lack of mechanism basedtoxicity in vertebrate organisms. The present specification disclosesisolation of a cDNA clone from the cat flea Ctenocephalides felis (CfGluCl-1)that encodes a L-glutamate-gated chloride channel. Heterologous expression ofCfGluCl-1 cRNA in Xenopus oocytes results in robust expression of a L-glutamate-gated chloride current and the channel is activated and potentiatedby avermectins. The expression of CfGluCl-1 in a heterologous expressionsystem is useful to screens for novel GluCl channel agonists and antagonists.Additionally, this specification discloses improved methods of screening forGluCl channel modulators.