Generation and regulation of the cell resting membrane potential - implications for function

细胞静息膜电位的产生和调节——对功能的影响

• 批准号: 1803030
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1803030
• 关键词: Generation; regulation; cell; resting; membrane

All cells have a resting membrane potential (RMP), due to the unequal ionic distribution across the membrane. Cellular integrity and function is closely coupled to the RMP with key processes including, for example, proliferation, secretion, and migration triggered by changes in membrane voltage. Hence, manipulation of the cell RMP has applications for health and disease, for example in cancer where cells have been shown to have RMPs that differ from their normal, healthy counterparts. The cell RMP is most readily recorded by microelectrode methods while specific fluorophores have been developed that measure ion concentrations within cells. Working with researchers equipped with expertise in electrophysiology, cell culture and live-cell fluorescence imaging, the aim of this rotation is to enable the student to sample these cutting-edge methodologies. The RMP in various cell lines will be measured in response to altered ionic gradients across the membrane to compare theoretical and experimental values. The dominant ionic species contributing to the cell RMP will also be determined using well-characterised ion channel blockers. A component of the training will involve the use of live-cell confocal imaging (at QMC) using known fluorophores that track potassium ions. Understanding key concepts of membrane biophysics will enable deeper mechanistic insight into thegeneration of the RMP and manipulation of cellular function.

由于跨膜离子分布不均匀，所有细胞都具有静息膜电位 (RMP)。细胞完整性和功能与 RMP 的关键过程密切相关，包括由膜电压变化触发的增殖、分泌和迁移等。因此，细胞 RMP 的操纵在健康和疾病方面都有应用，例如在癌症中，细胞已被证明具有与其正常、健康对应细胞不同的 RMP。细胞 RMP 最容易通过微电极方法记录，同时已经开发出测量细胞内离子浓度的特定荧光团。与具备电生理学、细胞培养和活细胞荧光成像专业知识的研究人员合作，这次轮换的目的是使学生能够体验这些尖端方法。将根据跨膜离子梯度的改变来测量各种细胞系中的 RMP，以比较理论值和实验值。有助于细胞 RMP 的主要离子种类也将使用充分表征的离子通道阻滞剂来确定。培训的一个组成部分将涉及使用活细胞共聚焦成像（在 QMC），该成像使用已知的追踪钾离子的荧光团。了解膜生物物理学的关键概念将使我们能够更深入地了解 RMP 的生成和细胞功能的操纵。