A Novel and Functionally Diverse Class of Acetylcholine-Gated Ion Channels.
A Novel and Functionally Diverse Class of Acetylcholine-Gated Ion Channels.
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DOI：
10.1523/jneurosci.1516-22.2022
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发表时间：
2023-02-15
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影响因子：
--
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中科院分区：
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快速胆碱能神经传递是由乙酰胆碱门控离子通道介导的；特别是，兴奋性烟碱乙酰胆碱受体在几乎所有神经系统中都发挥着既定的作用。在一些无脊椎动物门中也发现了乙酰胆碱门控抑制通道，但它们在神经系统中的作用尚不清楚。我们报告了秀丽隐杆线虫中存在多种具有不同配体激活特性的新抑制离子通道。我们确定了三个通道：LGC-40、LGC-57 和 LGC-58，其主要配体是胆碱而不是乙酰胆碱，以及真正的多模式通道 LGC-39 的第一个证据，它由胆碱能和胺能配体激活。利用我们新的配体-受体对，我们发现雌雄同体神经系统中的单个神经元表达兴奋性和抑制性通道的惊人程度，不仅表达乙酰胆碱，还表达其他主要神经递质。这项研究中提出的结果为了解大量多样的配体门控离子通道库在解剖学上紧凑的神经系统中产生复杂性的潜在进化益处提供了新的见解。意义声明在这里，我们描述了线虫秀丽隐杆线虫中胆碱能信号的多样性。我们鉴定并表征了一个新的配体门控离子通道家族，并表明它们优先由胆碱而不是乙酰胆碱门控，并在神经系统中广泛表达。有趣的是，我们还确定了一种由化学上不同的配体（包括乙酰胆碱和胺能配体）门控的通道。通过利用我们对这些配体门控离子通道的新知识，我们建立了一个模型来预测线虫连接组中的突触极性。该模型可用于生成神经回路功能的假设。
Fast cholinergic neurotransmission is mediated by acetylcholine-gated ion channels; in particular, excitatory nicotinic acetylcholine receptors play well established roles in virtually all nervous systems. Acetylcholine-gated inhibitory channels have also been identified in some invertebrate phyla, yet their roles in the nervous system are less well understood. We report the existence of multiple new inhibitory ion channels with diverse ligand activation properties in Caenorhabditis elegans. We identify three channels, LGC-40, LGC-57, and LGC-58, whose primary ligand is choline rather than acetylcholine, as well as the first evidence of a truly polymodal channel, LGC-39, which is activated by both cholinergic and aminergic ligands. Using our new ligand–receptor pairs we uncover the surprising extent to which single neurons in the hermaphrodite nervous system express both excitatory and inhibitory channels, not only for acetylcholine but also for the other major neurotransmitters. The results presented in this study offer new insight into the potential evolutionary benefit of a vast and diverse repertoire of ligand-gated ion channels to generate complexity in an anatomically compact nervous system. SIGNIFICANCE STATEMENT Here we describe the diversity of cholinergic signaling in the nematode Caenorhabditis elegans. We identify and characterize a novel family of ligand-gated ion channels and show that they are preferentially gated by choline rather than acetylcholine and expressed broadly in the nervous system. Interestingly, we also identify one channel gated by chemically diverse ligands including acetylcholine and aminergic ligands. By using our new knowledge of these ligand-gated ion channels, we built a model to predict the synaptic polarity in the C. elegans connectome. This model can be used for generating hypotheses on neural circuit function.
胆碱肌肉烟碱受体的块表明，激活和脱敏的门是不同的分子实体。
DOI：
10.1085/jgp.200509437
发表时间：
2006-06
期刊：
The Journal of general physiology
影响因子：
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作者：
Purohit Y;Grosman C
通讯作者：
Grosman C
影响因子：
4.3
作者：
Rakowski F;Karbowski J
通讯作者：
Karbowski J
影响因子：
2.9
作者：
Bondarenko, Vasyl;Targowska-Duda, Katarzyna M.;Jozwiak, Krzysztof;Tang, Pei;Arias, Hugo R.
通讯作者：
Arias, Hugo R.