Sneyd J, Tsaneva-Atanasova K, Bruce J I E, Straub S V, Giovannucci D R, Yule D I
Department of Mathematics, University of Auckland, Auckland, New Zealand.
Biophys J. 2003 Sep;85(3):1392-405. doi: 10.1016/S0006-3495(03)74572-X.
We construct a mathematical model of Ca(2+) wave propagation in pancreatic and parotid acinar cells. Ca(2+) release is via inositol trisphosphate receptors and ryanodine receptors that are distributed heterogeneously through the cell. The apical and basal regions are separated by a region containing the mitochondria. In response to a whole-cell, homogeneous application of inositol trisphosphate (IP(3)), the model predicts that 1), at lower concentrations of IP(3), the intracellular waves in pancreatic cells begin in the apical region and are actively propagated across the basal region by Ca(2+) release through ryanodine receptors; 2), at higher [IP(3)], the waves in pancreatic and parotid cells are not true waves but rather apparent waves, formed as the result of sequential activation of inositol trisphosphate receptors in the apical and basal regions; 3), the differences in wave propagation in pancreatic and parotid cells can be explained in part by differences in inositol trisphosphate receptor density; 4), in pancreatic cells, increased Ca(2+) uptake by the mitochondria is capable of restricting Ca(2+) responses to the apical region, but that this happens only for a relatively narrow range of [IP(3)]; and 5), at higher [IP(3)], the apical and basal regions of the cell act as coupled Ca(2+) oscillators, with the basal region partially entrained to the apical region.
我们构建了一个胰腺和腮腺腺泡细胞中Ca(2+)波传播的数学模型。Ca(2+)通过肌醇三磷酸受体和雷诺丁受体释放,这些受体在细胞内分布不均。顶端区域和基底区域被一个含有线粒体的区域隔开。对于全细胞均匀施加肌醇三磷酸(IP(3))的情况,该模型预测:1),在较低浓度的IP(3)下,胰腺细胞内的波起始于顶端区域,并通过雷诺丁受体释放的Ca(2+)在基底区域积极传播;2),在较高的[IP(3)]时,胰腺和腮腺细胞中的波不是真正的波,而是表观波,是顶端和基底区域的肌醇三磷酸受体顺序激活的结果;3),胰腺和腮腺细胞中波传播的差异部分可以通过肌醇三磷酸受体密度的差异来解释;4),在胰腺细胞中,线粒体增加的Ca(2+)摄取能够将Ca(2+)反应限制在顶端区域,但这仅在相对较窄的[IP(3)]范围内发生;5),在较高的[IP(3)]时,细胞的顶端和基底区域作为耦合的Ca(2+)振荡器,基底区域部分被顶端区域带动。