Control of calcium oscillations by membrane fluxes

It is known that Ca2+ influx plays an important role in the modulation of inositol trisphosphate-generated Ca2+ oscillations, but controversy over the mechanisms underlying these effects exists. In addition, the effects of blocking membrane transport or reducing Ca2+ entryvaryfrom one cell typeto another; in somecell types oscillations persist in the absence of Ca2+ entry (although theirfrequency is affected), whereas in other cell types oscillations depend on Ca2+ entry. We present theoretical and experimental evidence that membrane transport can control oscillations by controlling the total amount of Ca2+ in the cell (the Ca2+ load). Our model predicts that the cell can be balanced at a point where small changes in the Ca2+ load can move the cell into or out of oscillatory regions, resulting in the appearance or disappearance of oscillations. Our theoretical predictions are verified by experimental results from HEK293 cells. We predict that the role of Ca2+ influx during an oscillation is to replenish the Ca2+ load of the cell. Despite this prediction, even during the peak of an oscillation the cell or the encloplasmic reticulum may not be measurably depleted of Ca2+.