Sneyd James, Crampin Edmund, Yule David
Department of Mathematics, University of Auckland, New Zealand.
Systems Biology Laboratory, Melbourne School of Engineering, University of Melbourne, Australia & NICTA Victoria Research Laboratory, Australia.
Math Biosci. 2014 Nov;257:69-79. doi: 10.1016/j.mbs.2014.06.017. Epub 2014 Jul 8.
We review a multiscale model of saliva secretion, describing in brief how the model is constructed and what we have so far learned from it. The model begins at the level of inositol trisphosphate receptors (IPR), and proceeds through the cellular level (with a model of acinar cell calcium dynamics) to the multicellular level (with a model of the acinus), finally to a model of a saliva production unit that includes an acinus and associated duct. The model at the level of the entire salivary gland is not yet completed. Particular results from the model so far include (i) the importance of modal behaviour of IPR, (ii) the relative unimportance of Ca(2+) oscillation frequency as a controller of saliva secretion, (iii) the need for the periodic Ca(2+) waves to be as fast as possible in order to maximise water transport, (iv) the presence of functional K(+) channels in the apical membrane increases saliva secretion, (v) the relative unimportance of acinar spatial structure for isotonic water transport, (vi) the prediction that duct cells are highly depolarised, (vii) the prediction that the secondary saliva takes at least 1mm (from the acinus) to reach ionic equilibrium. We end with a brief discussion of future directions for the model, both in construction and in the study of scientific questions.
我们回顾了唾液分泌的多尺度模型，简要描述了该模型的构建方式以及我们目前从该模型中学到的内容。该模型从肌醇三磷酸受体（IPR）层面开始，经过细胞层面（腺泡细胞钙动力学模型）到多细胞层面（腺泡模型），最后到一个包含腺泡和相关导管的唾液生成单元模型。整个唾液腺层面的模型尚未完成。到目前为止，该模型的具体成果包括：（i）IPR模态行为的重要性；（ii）Ca(2+)振荡频率作为唾液分泌控制器相对不重要；（iii）周期性Ca(2+)波要尽可能快以实现水运输最大化；（iv）顶端膜中功能性K(+)通道的存在会增加唾液分泌；（v）腺泡空间结构对等渗水运输相对不重要；（vi）预测导管细胞高度去极化；（vii）预测次级唾液从腺泡开始至少需要1毫米才能达到离子平衡。我们最后简要讨论了该模型在构建和科学问题研究方面的未来方向。
