Quantitative analysis of local calcium release across cell types

Icahn School Of Medicine At Mount Sinai, New York NY

Investigators

Abstract

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.