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Updated: Jun 29, 2026
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Published on: August 27, 2011
Altered ivermectin pharmacology and defective visual system in Drosophila mutants for histamine receptor HCLB
Shazie Yusein1, Nadya Velikova, Petia Kupenova
1Department of Molecular Neurobiology, Institute of Molecular Biology, 1113, Sofia, Bulgaria.
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.
Insights
The Drosophila histamine-gated chloride channel B (hclB) is a target for ivermectin. Mutants reveal hclB
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- The Drosophila gene hclB encodes a histamine-gated chloride channel.
- This channel can be activated by the neurotoxin ivermectin in vitro.
Purpose of the Study:
- To investigate the in vivo role of the hclB gene.
- To identify hclB as a target for ivermectin in Drosophila melanogaster.
Main Methods:
- Identification of two novel hclB mutants (hclB (T1) and hclB (T2)) with distinct mutations.
- Survival studies comparing ivermectin sensitivity between mutants and wild-type flies.
- Electroretinogram recordings to assess synaptic transmission in the visual pathway.
Main Results:
- hclB (T1) mutants showed increased ivermectin sensitivity, while hclB (T2) mutants exhibited resistance.
- Mutants displayed altered synaptic transmission in the visual pathway, evidenced by enlarged electroretinogram peak amplitudes.
- Ivermectin treatment dose-dependently suppressed synaptic signals in an allele-specific manner.
Conclusions:
- HCLB is an essential in vivo target for ivermectin in Drosophila.
- The HCLB protein plays a significant role in the visual pathway's synaptic transmission.
