Unusual functional properties of homo- and heteromultimeric histamine-gated chloride channels of Drosophila melanogaster:: spontaneous currents and dual gating by GABA and histamine

Histamine acts as a neurotransmitter of photoreceptors in insects and other arthropods, where it directly activates a chloride channel and mediates rapid inhibitory responses. Homo- and heteromultimeric histamine-gated ion channels formed by HisC1-alpha2 or HisC1-alpha1 + alpha2 subunits from Drosophila melanogaster were characterized by two-electrode voltage-clamp measurements of functionally expressed ion channels in Xenopus laevis oocytes. The sensitivity of heteromultimeric histamine receptors with an EC50 of 2.3 muM is lower than that of either homomultimeric receptor. They can be further distinguished from the homomultimeric channels by their reduced sensitivity to D-tubocurarine. Heteromultimeric channels generate a spontaneous current in the absence of any agonist. This spontaneous current can be blocked in the absence of an agonist by D-tubocurarine and the histamine antagonists cimetidine, thioperamide and pyrilamine. Homomultimeric HisC1-alpha2 channels are dually gated by histamine (IC50 = 9.4 muM) and GABA (IC50 = 1.0 mM), both of which are full agonists. The action of both agonists can be blocked with comparable IC50 values by the histamine antagonists cimetidine, thioperamide and pyrilamine but not by the GABA antagonist bicuculline. Picrotoxin blocked with an IC50 of 403 muM. Our data show that histamine and GABA act on the same ion channel, which thus might function as a site of integration of the action of different neurotransmitters. (C) 2004 Elsevier Ireland Ltd. All rights reserved.