Sneyd J, Tsaneva-Atanasova K, Yule D I, Thompson J L, Shuttleworth T J
Department of Mathematics, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1392-6. doi: 10.1073/pnas.0303472101. Epub 2004 Jan 20.
It is known that Ca(2+) influx plays an important role in the modulation of inositol trisphosphate-generated Ca(2+) oscillations, but controversy over the mechanisms underlying these effects exists. In addition, the effects of blocking membrane transport or reducing Ca(2+) entry vary from one cell type to another; in some cell types oscillations persist in the absence of Ca(2+) entry (although their frequency is affected), whereas in other cell types oscillations depend on Ca(2+) entry. We present theoretical and experimental evidence that membrane transport can control oscillations by controlling the total amount of Ca(2+) in the cell (the Ca(2+) load). Our model predicts that the cell can be balanced at a point where small changes in the Ca(2+) 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 Ca(2+) influx during an oscillation is to replenish the Ca(2+) load of the cell. Despite this prediction, even during the peak of an oscillation the cell or the endoplasmic reticulum may not be measurably depleted of Ca(2+).
已知钙离子内流在三磷酸肌醇引发的钙离子振荡调节中起重要作用，但对于这些效应背后的机制仍存在争议。此外，阻断膜转运或减少钙离子内流的效应因细胞类型而异；在某些细胞类型中，即使没有钙离子内流振荡仍会持续（尽管其频率会受到影响），而在其他细胞类型中，振荡则依赖于钙离子内流。我们提供了理论和实验证据，表明膜转运可通过控制细胞内钙离子总量（钙离子负荷）来控制振荡。我们的模型预测，细胞可在一个平衡点上保持平衡，此时钙离子负荷的微小变化可使细胞进入或离开振荡区域，从而导致振荡的出现或消失。我们的理论预测得到了来自人胚肾293细胞的实验结果的验证。我们预测，振荡过程中钙离子内流的作用是补充细胞的钙离子负荷。尽管有此预测，但即使在振荡峰值期间，细胞或内质网中的钙离子也可能没有明显耗尽。
