Department of Mathematics, The University of Auckland, Auckland, New Zealand.
Biophys J. 2013 Sep 3;105(5):1133-42. doi: 10.1016/j.bpj.2013.07.034.
Calcium puffs are local transient Ca(2+) releases from internal Ca(2+) stores such as the endoplasmic reticulum or the sarcoplasmic reticulum. Such release occurs through a cluster of inositol 1,4,5-trisphosphate receptors (IP3Rs). Based on the IP3R model (which is determined by fitting to stationary single-channel data) and nonstationary single-channel data, we construct a new IP3R model that includes time-dependent rates of mode switches. A point-source model of Ca(2+) puffs is then constructed based on the new IP3R model and is solved by a hybrid Gillespie method with adaptive timing. Model results show that a relatively slow recovery of an IP3R from Ca(2+) inhibition is necessary to reproduce most of the experimental outcomes, especially the nonexponential interpuff interval distributions. The number of receptors in a cluster could be severely underestimated when the recovery is sufficiently slow. Furthermore, we find that, as the number of IP3Rs increases, the average duration of puffs initially increases but then becomes saturated, whereas the average decay time keeps increasing linearly. This gives rise to the observed asymmetric puff shape.
钙波是细胞内钙库（如内质网或肌浆网）局部短暂的 Ca(2+)释放。这种释放是通过一组肌醇 1,4,5-三磷酸受体（IP3R）发生的。基于 IP3R 模型（通过拟合静态单通道数据确定）和非静态单通道数据，我们构建了一个新的包含模式转换时变速率的 IP3R 模型。然后基于新的 IP3R 模型构建了一个钙波的点源模型，并使用具有自适应时间的混合 Gillespie 方法进行求解。模型结果表明，为了再现大多数实验结果，尤其是非指数间隔分布的钙波，需要从 Ca(2+)抑制中恢复相对缓慢的 IP3R。当恢复足够慢时，簇中的受体数量可能会被严重低估。此外，我们发现，随着 IP3R 数量的增加，钙波的平均持续时间最初会增加，但随后会达到饱和，而平均衰减时间则保持线性增加。这导致了观察到的不对称的钙波形状。
