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The Journal of Neuroscience, July 16, 2008, 28(29):7250-7259; doi:10.1523/JNEUROSCI.1654-08.2008

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Cellular/Molecular
Distinct Roles for Two Histamine Receptors (hclA and hclB) at the Drosophila Photoreceptor Synapse

Antonios Pantazis,¹ Ashvina Segaran,¹ Che-Hsiung Liu,¹ Anton Nikolaev,² Jens Rister,³ Andreas S. Thum,³ Thomas Roeder,⁴ Eugene Semenov,⁵ Mikko Juusola,² and Roger C. Hardie¹

¹Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3DY, United Kingdom, ²Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom, ³Lehrstuhl für Genetik und Neurobiologie, Universität Würzburg, 97074 Würzburg, Germany, ⁴Zoologisches Institut, Abteilung Zoophysiologie, Christian-Albrechts-Universität, D-24098 Kiel, Germany, and ⁵Department of Molecular Neurobiology, Drosophila Neurogenetics Laboratory, Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria

Correspondence should be addressed to Roger C. Hardie, Department of Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Email: rch14{at}cam.ac.uk

Histamine (HA) is the photoreceptor neurotransmitter in arthropods, directly gating chloride channels on large monopolar cells (LMCs), postsynaptic to photoreceptors in the lamina. Two histamine-gated channel genes that could contribute to this channel in Drosophila are hclA (also known as ort) and hclB (also known as hisCl1), both encoding novel members of the Cys-loop receptor superfamily. Drosophila S2 cells transfected with these genes expressed both homomeric and heteromeric histamine-gated chloride channels. The electrophysiological properties of these channels were compared with those from isolated Drosophila LMCs. HCLA homomers had nearly identical HA sensitivity to the native receptors (EC₅₀ = 25 µM). Single-channel analysis revealed further close similarity in terms of single-channel kinetics and subconductance states (25, 40, and 60 pS, the latter strongly voltage dependent). In contrast, HCLB homomers and heteromeric receptors were more sensitive to HA (EC₅₀ = 14 and 1.2 µM, respectively), with much smaller single-channel conductances (4 pS). Null mutations of hclA (ort^US6096) abolished the synaptic transients in the electroretinograms (ERGs). Surprisingly, the ERG "on" transients in hclB mutants transients were approximately twofold enhanced, whereas intracellular recordings from their LMCs revealed altered responses with slower kinetics. However, HCLB expression within the lamina, assessed by both a GFP (green fluorescent protein) reporter gene strategy and mRNA tagging, was exclusively localized to the glia cells, whereas HCLA expression was confirmed in the LMCs. Our results suggest that the native receptor at the LMC synapse is an HCLA homomer, whereas HCLB signaling via the lamina glia plays a previously unrecognized role in shaping the LMC postsynaptic response.

Key words: ligand-gated ion channel; chloride channel; retina; vision; LMC; lamina; glia; ort

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Received April 16, 2008; revised May 29, 2008; accepted June 2, 2008.

Correspondence should be addressed to Roger C. Hardie, Department of Physiology, Development, and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Email: rch14{at}cam.ac.uk

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