Auckland Bioengineering Institute, The University of Auckland Auckland, New Zealand.
Front Physiol. 2011 Jul 4;2:29. doi: 10.3389/fphys.2011.00029. eCollection 2011.
Gastrointestinal motility research is progressing rapidly, leading to significant advances in the last 15 years in understanding the cellular mechanisms underlying motility, following the discovery of the central role played by the interstitial cells of Cajal (ICC). As experimental knowledge of ICC physiology has expanded, biophysically based modeling has become a valuable tool for integrating experimental data, for testing hypotheses on ICC pacemaker mechanisms, and for applications in in silico studies including in multiscale models. This review is focused on the cellular electrophysiology of ICC. Recent evidence from both experimental and modeling domains have called aspects of the existing pacemaker theories into question. Therefore, current experimental knowledge of ICC pacemaker mechanisms is examined in depth, and current theories of ICC pacemaking are evaluated and further developed. Existing biophysically based ICC models and their physiological foundations are then critiqued in light of the recent advances in experimental knowledge, and opportunities to improve these models are identified. The review concludes by examining several potential clinical applications of biophysically based ICC modeling from the subcellular through to the organ level, including ion channelopathies and ICC network degradation.
胃肠动力研究进展迅速，在过去的 15 年中，随着 Cajal 间质细胞（ICC）在运动中的核心作用的发现，对运动背后的细胞机制的理解取得了重大进展。随着对 ICC 生理学的实验知识的扩展，基于生物物理的建模已成为整合实验数据、测试 ICC 起搏机制假设以及在包括多尺度模型在内的计算研究中应用的有价值的工具。这篇综述专注于 ICC 的细胞电生理学。来自实验和建模领域的最新证据对现有的起搏理论提出了质疑。因此，深入研究了 ICC 起搏机制的当前实验知识，并对 ICC 起搏理论进行了评估和进一步发展。然后，根据最近在实验知识方面的进展，对现有的基于生物物理的 ICC 模型及其生理基础进行了批判性分析，并确定了改进这些模型的机会。该综述最后考察了从亚细胞到器官水平的基于生物物理的 ICC 建模的几个潜在临床应用，包括离子通道病和 ICC 网络退化。
