Gastrointestinal motility is based on the rhythmic activity of interstitial cells of Cajal (ICCs). The ICC rhythm generation relies upon characteristic Ca2+-handling mechanisms that involve voltage-gated Ca2+ channels, pumps and exchangers located in the plasma membrane, endoplasmic reticulum (ER), and mitochondria. Mutations, overexpression, and genetic knockdowns of the plasma membrane calcium ATPase (PMCA) pumps have been shown to disrupt calcium signaling and to cause disorders in other cell systems. Using an ICC biophysical model, we investigated the effects of PMCA pump upregulation in ICC rhythm generation. We found that, depending on the PMCA maximum pumping rate, the ICC model generates voltage and Ca2+ oscillations with different characteristics or becomes silent. The model predicts the coexistence of activity regimes near a canonical set of the parameters. One of these regimes is a silent regime that would indicate gastric dysmotility.

中文翻译：

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质膜 Ca2+-ATPase 泵在 Cajal 间质细胞节律生成调节中的作用：一项计算研究

胃肠动力基于 Cajal (ICC) 间质细胞的节律活动。ICC 节律的产生依赖于特征性的 Ca2+ 处理机制，涉及电压门控 Ca2+ 通道、泵和位于质膜、内质网 (ER) 和线粒体中的交换器。已经证明质膜钙 ATP 酶 (PMCA) 泵的突变、过度表达和基因敲低会破坏钙信号传导并导致其他细胞系统的紊乱。我们使用 ICC 生物物理模型研究了 PMCA 泵上调对 ICC 节律生成的影响。我们发现，根据 PMCA 最大泵速，ICC 模型会产生具有不同特征的电压和 Ca2+ 振荡或变得无声。该模型预测了一组规范参数附近活动状态的共存。这些方案之一是表明胃动力障碍的无声方案。