Single Ion Channel Determines Phenotype from Genotype

随着科学在分子水平上发现更多关于细胞过程的信息，将这些发现整合到生理系统中的任务变得越来越有针对性。细胞心脏电生理学的许多实验都是在分子水平上进行的，需要整合到整个细胞、多细胞组织和心脏的背景下。基于生物物理学的计算机模型整合了分子水平上的发现，以预测宏观结果，在完成这一任务方面是有用的。在这里，我们建议构建在心室肌细胞中产生动作电位的离子通道的分子水平模型。这些模型将提供对这些通道在健康和疾病状态下动作电位产生中的作用的洞察。这一认识将为心律失常的治疗和心脏性猝死的预防提供机制基础。

As science uncovers more information about cellular processes at the molecular level, the task of integrating such findings into the physiological system becomes increasingly pertinent. Many experiments in cellular cardiac electrophysiology are conducted at a molecular level and need to be integrated into the context of the whole cell, the multicellular tissue, and the heart. Biophysically based computer models that integrate findings on the molecular level to predict macroscopic results are useful in accomplishing this task. Here we propose to construct molecular level models of ion channels that generate the action potential in ventricular myocytes. These models will provide insight into the roles of these channels in action potential generation in both healthy and diseased states. Moreover, this insight will give a mechanistic basis for the treatment of cardiac arrhythmias and prevention of sudden cardiac death.