Altered ivermectin pharmacology and defective visual system in <Emphasis Type="Italic">Drosophila</Emphasis> mutants for histamine receptor HCLB |
| |
Authors: | Shazie Yusein Nadya Velikova Petia Kupenova Roger Hardie Adrian Wolstenholme Eugene Semenov |
| |
Institution: | (1) Department of Molecular Neurobiology, Institute of Molecular Biology, 1113 Sofia, Bulgaria;(2) Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge, CB2 3DY, UK;(3) Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK |
| |
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.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
An erratum to this article can be found at |
| |
Keywords: | Drosophila Histamine-gated chloride channel Mutations Ivermectin Vision |
本文献已被 PubMed SpringerLink 等数据库收录! |
|