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

由于膜上离子分布不均匀，所有细胞都有静止膜电位(RMP)。细胞的完整性和功能与RMP密切相连，关键过程包括，例如，由膜电压变化引发的增殖、分泌和迁移。因此，对细胞RMP的操纵在健康和疾病方面都有应用，例如在癌症中，细胞的RMP已被证明具有与正常健康细胞不同的RMP。细胞RMP最容易被微电极方法记录，而特定的荧光团已经被开发出来测量细胞内的离子浓度。与配备了电生理学、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采样这些尖端方法。不同细胞系的RMP将根据膜上离子梯度的变化进行测量，以比较理论值和实验值。构成细胞RMP的主要离子物种也将使用特征良好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)，使用已知的跟踪钾离子的荧光团。了解膜生物物理学的关键概念将使我们能够更深入地从机制上洞察RMP的产生和细胞功能的操纵。

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.