Single Ion Channel Determines Phenotype from Genotype

单离子通道根据基因型确定表型

• 批准号: 6645360
• 负责人: JONATHAN R SILVA
• 金额: $ 3.16万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2004-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6645360
• 关键词: action potentials; biophysics; calcium channel; cardiac myocytes; cell biology; chemical binding; computer simulation; electrophysiology; gene mutation; genotype; heart ventricle; membrane channels; model design /development; molecular biology; phenotype; potassium channel; predoctoral investigator; sodium channel

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.

随着科学在分子水平上发现有关细胞过程的更多信息，将这种发现纳入生理系统的任务变得越来越相关。细胞心电生理学中的许多实验都是在分子水平进行的，需要整合到整个细胞，多细胞组织和心脏的背景中。基于生物物理的计算机模型，这些模型在分子水平上整合发现以预测宏观结果可用于完成此任务。在这里，我们建议构建离子通道的分子水平模型，从而在心室肌细胞中产生动作电位。这些模型将洞悉这些渠道在健康状态和患病状态下的动作潜力产生中的作用。此外，这种见解将为心律不齐和预防心脏猝死提供机械基础。