The ACC-1 family of cys-loop receptors are ligand-gated chloride channels sensitive to acetylcholine (ACh), and are only present in invertebrates. Studies of this family of inhibitory receptors has provided insight into how they bind and respond to ACh in a manner vastly different from nicotinic acetylcholine receptors and appear to be present in tissues that are relevant to anthelmintic action. Here, we have identified two members of the ACC-1 family from the parasitic nematode Haemonchus contortus, Hco-LGC-46 and Hco-ACC-4. Hco-LGC-46 is an ACC subunit that has never been previously expressed and pharmacologically characterized. We found that Hco-LGC-46 when expressed in Xenopus laevis oocytes forms a functional homomeric channel that is responsive to the cholinergic agonists ACh and methylcholine. hco-lgc-46 expressed in a C. elegans lgc-46 null strain (ok2900) suppressed hypersensitivity to aldicarb in a manner similar to cel-lgc-46. It was also found that Hco-LGC-46 assembles with Hco-ACC-1 and produces a receptor that is over 5-fold more sensitive to ACh and responds to the cholinergic agonists methycholine and carbachol. In contrast, the co-expression of Hco-LGC-46 with Hco-ACC-4 resulted in non-functional channels in oocytes. Hco-ACC-4 also appears to form heteromeric channels with a previously characterized subunit, Hco-ACC-2. Co-expression of Hco-ACC-4 with Hco-ACC-2 resulted in a functional heteromeric channel with an EC₅₀ value similar to that of the Hco-ACC-2 homomeric channel. However, the maximum currents generated in the ACC-4/ACC-2 channel were significantly (p < 0.005) lower than those from the ACC-2 homomeric channel. Overall, this is the first report confirming that lgc-46 encodes an acetylcholine-gated chloride channel which when co-expressed with acc-4 results in reduced receptor function or trafficking in oocytes.

ACC-1 家族的 cys-loop 受体是对乙酰胆碱 (ACh) 敏感的配体门控氯离子通道，仅存在于无脊椎动物中。对这一抑制受体家族的研究提供了对它们如何以与烟碱乙酰胆碱受体截然不同的方式结合和响应 ACh 的见解，并且似乎存在于与驱虫作用相关的组织中。在这里，我们从寄生线虫Haemonchus contortus中鉴定出 ACC-1 家族的两个成员，Hco-LGC-46 和 Hco-ACC-4。Hco-LGC-46 是一种 ACC 亚基，以前从未表达过和药理学特征。我们发现 Hco-LGC-46 在非洲爪蟾中表达时卵母细胞形成对胆碱能激动剂 ACh 和甲基胆碱有反应的功能性同源通道。在秀丽隐杆线虫 lgc-46无效菌株 ( ok2900 )中表达的hco-lgc-46以类似于cel-lgc-46的方式抑制对涕灭威的超敏反应. 还发现 Hco-LGC-46 与 Hco-ACC-1 组装并产生对 ACh 敏感超过 5 倍的受体，并对胆碱能激动剂甲胆碱和卡巴胆碱有反应。相反，Hco-LGC-46 与 Hco-ACC-4 的共表达导致卵母细胞中的非功能性通道。Hco-ACC-4 似乎也与先前表征的亚基 Hco-ACC-2 形成异聚通道。Hco-ACC-4 与Hco-ACC-2 的共表达导致具有与Hco-ACC-2 同源通道相似的EC _{50值的功能性异聚通道。}然而，在 ACC-4/ACC-2 通道中产生的最大电流显着 (p < 0.005) 低于来自 ACC-2 同源通道的最大电流。总的来说，这是第一份确认lgc-46编码乙酰胆碱门控氯离子通道，当与acc-4共表达时，会导致受体功能降低或卵母细胞运输。