Quantitative analysis of local calcium release across cell types

跨细胞类型局部钙释放的定量分析

• 批准号: 1615677
• 负责人: Eric Sobie
• 金额: $ 65.94万
• 依托单位: Icahn School of Medicine at Mount Sinai
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1615677&HistoricalAwards=false
• 关键词: Quantitative; analysis; local; calcium; release

The release of calcium inside cells is critically important for such functions as muscle contraction (including heartbeat) and egg (oocyte) maturation. Calcium release signals are initiated by local events inside cells known as "sparks" or "puffs" and these lead to the release of calcium throughout the cell. This project will test whether the mechanisms that control calcium sparks and puffs are involved respectively in the physiological process of cell-wide calcium release in oocytes and the cell-wide release of calcium in heart cells which, if not tightly controlled, can lead to problems with uncoordinated contractions of heart muscle (irregular heart beat.) Undergraduate students from the City University of New York will be engaged with this research project, learning concepts of both cell biology and the mathematical modeling of biological processes. The studies carried out by undergraduates will be included in a "Teaching Resource" publication that will make widely available teaching materials to which undergraduates have made major contributions. The hypothesis to be tested is that mechanisms of puff termination will encourage physiological, cell-wide Ca2+ release in oocytes whereas spark termination mechanisms will suppress pathological cell-wide Ca2+ release in cardiac myocytes. In this project, simulations will be carried out to evaluate how the mechanisms of activation and termination of sparks and puffs influence event variability within release sites and between sites. The relationships between Ca2+ sparks, Ca2+ puffs, and the transition from local events to cell-wide Ca2+ waves will also be simulated, and modeling predictions will be tested experimentally (using Xenopus oocytes and rat cardiac myocytes) by measuring variability in Ca2+ sparks,variability in Ca2+ puffs, and how this influences the spark/puff to Ca2+ wave transition.

细胞内钙的释放对于肌肉收缩（包括心跳）和卵（卵母细胞）成熟等功能至关重要。钙释放信号是由细胞内的局部事件启动的，称为“火花”或“泡芙”，这些事件导致整个细胞释放钙。该项目将测试控制钙火花和喷流的机制是否分别涉及卵母细胞中细胞范围的钙释放和心脏细胞中细胞范围的钙释放的生理过程，如果不严格控制，可能导致心肌收缩不协调的问题（不规则心跳）。来自纽约城市大学的本科生将参与这一研究项目，学习细胞生物学和生物过程数学建模的概念。本科生进行的研究将列入“教学资源”出版物，该出版物将广泛提供本科生作出重大贡献的教学材料。要测试的假设是，喷终止机制将鼓励生理，细胞范围内的Ca 2+释放卵母细胞，而火花终止机制将抑制病理细胞范围内的Ca 2+释放心肌细胞。在本项目中，将进行模拟，以评估火花和喷烟的激活和终止机制如何影响释放地点内和地点之间的事件变异性。还将模拟Ca 2+火花、Ca 2+喷流以及从局部事件到细胞范围内的Ca 2+波的过渡之间的关系，并通过测量Ca 2+火花的变异性、Ca 2+喷流的变异性以及这如何影响火花/喷流到Ca 2+波的过渡，对建模预测进行实验测试（使用非洲爪蟾卵母细胞和大鼠心肌细胞）。