학술논문

Altered ivermectin pharmacology and defective visual system in Drosophila mutants for histamine receptor HCLB
Document Type
Report
Source
Invertebrate Neuroscience. Dec, 2008, Vol. 8 Issue 4, p211, 12 p.
Subject
Ivermectin -- Physiological aspects
Drosophila -- Physiological aspects
Animal genetics -- Physiological aspects
Histamine -- Physiological aspects
Neurosciences -- Physiological aspects
Language
English
ISSN
1354-2516
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 .sup.T1) or a putative null mutation (W111*, allele hclB .sup.T2), as well as a novel splice form of the gene. In survival studies, hclB .sup.T1 mutants were more sensitive to ivermectin than wild-type, whereas hclB .sup.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.