Quantitative analysis of local calcium release across cell types

细胞内钙的释放对肌肉收缩（包括心跳）和卵子（卵母细胞）成熟等功能至关重要。钙释放信号是由细胞内被称为“火花”或“泡芙”的局部事件引发的，这些事件导致钙在整个细胞中释放。本项目将测试控制钙火花和钙泡的机制是否分别参与卵母细胞全细胞钙释放和心脏细胞全细胞钙释放的生理过程，如果控制不严格，可能导致心肌不协调收缩（不规则心跳）的问题。来自纽约城市大学的本科生将参与这个研究项目，学习细胞生物学的概念和生物过程的数学建模。本科生所进行的研究将被收录在“教学资源”刊物中，该刊物将广泛提供本科生作出主要贡献的教材。待验证的假设是，泡扑终止机制将促进卵母细胞中生理的、全细胞范围的Ca2+释放，而火花终止机制将抑制心肌细胞中病理的全细胞范围的Ca2+释放。在这个项目中，将进行模拟，以评估火花和气泡的激活和终止机制如何影响释放点内和点之间的事件变异性。Ca2+火花，Ca2+泡芙之间的关系，以及从局部事件到细胞范围内的Ca2+波的过渡也将被模拟，建模预测将通过测量Ca2+火花的变异性，Ca2+泡芙的变异性，以及这如何影响火花/泡芙到Ca2+波的过渡进行实验测试（使用爪蟾卵母细胞和大鼠心肌细胞）。

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.