Fine tuning the nicotinic receptor response via the lipid bilayer

通过脂质双层微调烟碱受体反应

• 批准号: RGPIN-2016-04973
• 负责人: Baenziger, John
• 金额: $ 3.21万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688785
• 关键词: Fine; tuning; nicotinic; receptor; response

Nerve cells in the brain communicate with each other at connections called synapses. At a synapse, small chemical neurotransmitters are released from the pres-synaptic terminus of one nerve cell to interact with receptors located in the post-synaptic membrane of another nerve cell. Upon binding to a receptor, the neurotransmitter elicits a structural change that leads to alteration of the environment inside the post-synaptic nerve cell. This change in intracellular environment usually leads to either the firing or the inhibition of firing in the post-synaptic nerve. ***Synapses are at the heart of complex neurological processes. For example, synapses can be strengthened to improve memory. On the other hand, altered synaptic transmission can lead to a variety of neurological disorders. Understanding how synapses are modulated is thus fundamental to understanding the human brain.****My lab is interested in the neurotransmitter receptors, called ligand-gated ion channels, that are located in post-synaptic membranes. The activities of these ligand-gated ion channels can be modulated by a variety of factors, including external compounds such as nicotine. We are interested in understanding how the lipids in the surrounding membrane influence function. Using a model system, we will characterize the lipids found in this environment and then test how these lipids influence ligand-gated ion channel function. Using sophisticated molecular biology, electrophysiology, and crystallography tools, we will test proposed mechanisms by which lipids alter function. The overarching goal is to understand the role of lipids modulating ligand-gated ion channel function under both normal and abnormal neurological conditions. This fundamental research will provide a basis to help understand complex neurological diseases, such as Alzheimer's Disease, etc. ***************

大脑中的神经细胞通过称为突触的连接相互通信。 在突触处，小的化学神经递质从一个神经细胞的突触前末端释放，以与位于另一个神经细胞的突触后膜中的受体相互作用。 当与受体结合时，神经递质引起结构变化，导致突触后神经细胞内环境的改变。 细胞内环境的这种变化通常导致突触后神经的放电或放电抑制。* 突触是复杂神经过程的核心。 例如，可以加强突触以提高记忆力。 另一方面，突触传递的改变会导致各种神经系统疾病。 因此，了解突触是如何被调节的是了解人类大脑的基础。我的实验室对神经递质受体很感兴趣，这种受体被称为配体门控离子通道，位于突触后膜上。 这些配体门控离子通道的活性可以由多种因素调节，包括外部化合物如尼古丁。 我们有兴趣了解周围膜中的脂质如何影响功能。 使用一个模型系统，我们将描述在这种环境中发现的脂质，然后测试这些脂质如何影响配体门控离子通道功能。 使用复杂的分子生物学，电生理学和晶体学工具，我们将测试脂质改变功能的机制。 总体目标是了解脂质在正常和异常神经系统条件下调节配体门控离子通道功能的作用。 这一基础研究将为帮助了解阿尔茨海默病等复杂的神经系统疾病提供基础。