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Modeling Ca2+ signals: understanding Ca2+ regulatory networks in cells - Ca2+ stores: endoplasmic reticulum, calcium oscillations

Part 2 of 3
Published on August 30, 2021   41 min

A selection of talks on Biochemistry

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0:05
We will next turn to multi-compartmental models and then describe several biologically relevant examples where calcium-dependent channel gating has a powerful effect on calcium dynamics.
0:18
Now, that we have outlined the basic approach for describing calcium dynamics in a cell with a single compartment. Let's now turn to a discussion of calcium stores. We will first discuss general concepts, followed by an analysis of a simple linear one-pool model that illustrates many of the basic effects that stores can have on calcium dynamics. Then we will describe interesting properties imparted to calcium signaling when stores express calcium channels that open in response to elevations in the cytosolic calcium concentration. There are two general cases that differ in terms of the direction in which calcium flows when these channels open, which is in turn determined by the driving force on calcium, as established by the specific transport systems that operate in the respective stores. In the first case, which is relevant to the endoplasmic reticulum, such channels make it possible for a store to support calcium-induced calcium release. In the second case, which is relevant to mitochondria, calcium-sensitive channels permit intracellular calcium uptake at a rate that is highly sensitive to the cytosolic calcium levels. Understanding how these stores individually contribute to calcium signaling is critical for understanding how they work together when operating simultaneously in the same cell.
1:31
Calcium stores are membrane delimited intracellular compartments that use specific calcium transport and buffering systems to regulate their intraluminal calcium levels. Examples include the endoplasmic reticulum, mitochondria, the nucleus, as well as other organelles such as the Golgi apparatus and secretory vesicles. We now have the basic conceptual tools for grappling with the effects of such stores on calcium dynamics. At a given instant in time, the impact of a store on the intracellular distribution of calcium depends on the net calcium flux between the store and the cytosol, which we call the inter-compartmental calcium flux, Js. This flux can mediate either a loss or gain of store calcium, in which case the store would be described as a source or sink respectively. In the same way that the interdepartmental calcium flux across the plasma membrane depends on the relative rates of transport via different transport systems. The direction and magnitude of Js depends on the relative rates of transport via pathways that mediate calcium uptake and release. Among the interesting features of calcium signaling stores are the following. First, net calcium uptake and release by a store affects cytosolic and intraluminal calcium levels interdependently, for example, net calcium release from a store which reduces intraluminal calcium levels, must also increase cytosolic calcium levels. Secondly, if stores act as sinks or sources during stimulation, they tend to act as sources or sinks after the stimulus ends as is pre-stimulus calcium distribution is restored.

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Modeling Ca2+ signals: understanding Ca2+ regulatory networks in cells - Ca2+ stores: endoplasmic reticulum, calcium oscillations

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