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

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Invertebrate Neuroscience

An Erratum to this article was published on 21 November 2008

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.

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Acknowledgments

We are grateful to Dr. Onik Medjelian (Actavis) for kind providing us with hydroxyzine. We thank Nely Balatcheva, Leny Markova and Margarita Sotirova for technical help. Flies Df(3R)E79/MRS were provided by Bloomington Drosophila Stock Center, USA. This study was supported by a collaborative research grant from the Wellcome Trust (a CRIG award GR075386MA to A. W. and E. S.).

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Authors and Affiliations

  1. Department of Molecular Neurobiology, Institute of Molecular Biology, 1113, Sofia, Bulgaria

    Shazie Yusein, Nadya Velikova, Petia Kupenova & Eugene Semenov

  2. Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge, CB2 3DY, UK

    Roger Hardie

  3. Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK

    Adrian Wolstenholme

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  1. Shazie Yusein
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  2. Nadya Velikova
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  6. Eugene Semenov
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Correspondence to Eugene Semenov.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s10158-008-0083-5

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10158_2008_78_MOESM1_ESM.eps

Intensity dependence of the photoreceptor component of the ERG. All symbols follow descriptions given to Figure 3. a OR/Df(3R)E79; b hclB T1/Df(3R)E79; c hclB T2/Df(3R)E79 (EPS 98 kb)

10158_2008_78_MOESM2_ESM.eps

The time-to-peak values of the transient components on ERGs from adult females of three genotypes. a and d OR/Df(3R)E79, b and e hclB T1/Df(3R)E79, c and f hclB T2/Df(3R)E79 (EPS 141 kb)

10158_2008_78_MOESM3_ESM.eps

Amplitudes of the photoreceptor component of the ERGs following treatment with ivermectin. a OR/Df(3R)E79, b hclB T1/Df(3R)E79, c hclB T2/Df(3R)E79 (EPS 104 kb)

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Yusein, S., Velikova, N., Kupenova, P. et al. Altered ivermectin pharmacology and defective visual system in Drosophila mutants for histamine receptor HCLB. Invert Neurosci 8, 211–222 (2008). https://doi.org/10.1007/s10158-008-0078-2

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