DNA MOLECULES ENCODING CTENOCEPHALIDES FELIS GLUTAMATE GATED CHLORIDE CHANNELS

摘要

To date, L-glutamate-gated chloride (GluC1) channels have been observed only in invertebrate organisms. Modulators of this channel (either agonists or antagonists) will interfere with neurotransmission. For example, agents such as avermectins activate the GluCl, causing paralysis due to blocking of neurotransmitter release, resulting in death of the organism. Because GluCl channels are invertebrate specific, they are excellent targets for the discovery of novel insecticides, anthelminths and parasiticides that will display a marked safety profile because of the lack of mechanism based toxicity in vertebrate organisms. The present specification discloses isolation of a cDNA clone from the cat flea Ctenocephalides felis (CfGluCl-1) that encodes a L-glutamate-gated chloride channel. Heterologous expression of CfGluCl-1 cRNA in Xenopus oocytes results in robust expression of a L-glutamate-gated chloride current and the channel is activated and potentiated by avermectins. The expression of CfGluCl-1 in a heterologous expression system is useful to screens for novel GluCl channel agonists and antagonists. Additionally, this specification discloses improved methods of screening for GluCl channel modulators.