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.

中文翻译：

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果蝇突变体中组胺受体HCLB的伊维菌素药理学改变和视觉系统缺陷。

果蝇基因hclB编码一个组胺门控的氯离子通道，在体外表达时可以被神经毒素伊维菌素激活。我们已经鉴定出两个新颖的hclB突变体，携带一个错义突变（P293S，等位基因hclB（T1））或推定的无效突变（W111 *，等位基因hclB（T2）），以及该基因的新型剪接形式。在存活研究中，hclB（T1）突变体对伊维菌素的敏感性高于野生型，而hclB（T2）的抗药性更高。来自两个突变体的视网膜电图记录显示瞬时成分的峰值幅度增大，表明视网膜光神经元与其靶细胞之间的突触传递发生改变。伊维菌素治疗以等位基因特异性方式严重影响或完全抑制了这些短暂成分。伊维菌素对突触信号的抑制作用是剂量依赖性的。这些结果确定了HCLB是黑腹果蝇中伊维菌素的重要体内靶标，并证明该蛋白参与了视觉途径。