Altered ivermectin pharmacology and defective visual system in Drosophila mutants for histamine receptor HCLB.

Abstract  The Drosophila gene hclB encodes a histamine-gated chloride channel, which can be activated by the neurotoxin ivermectin when expressed in vitro. We have identified two novel hclB mutants, carrying either a missense mutation (P293S, allele hclB T1 ) or a putative null mutation (W111*, allele hclB T2 ), as well as a novel splice form of the gene. In survival studies, hclB T1 mutants were more sensitive to ivermectin than wild-type, whereas hclB T2 were more resistant. Electroretinogram recordings from the two mutants exhibited enlarged peak amplitudes of the transient components, indicating altered synaptic transmission between retinal photoneurons and their target cells. Ivermectin treatment severely affected or completely suppressed these transient components in an allele-specific manner. This suppression of synaptic signals by ivermectin was dose-dependent. These results identify HCLB as an important in vivo target for ivermectin in Drosophila melanogaster, and demonstrate the involvement of this protein in the visual pathway. [ABSTRACT FROM AUTHOR]

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