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揭示了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重要。细胞心脏电生理学的许多实验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。基于生物病理学的计算机模型，整合分子水平上的发现，以预测宏观结果是有用的，在完成这项任务。在这里，我们建议建立分子水平的离子通道模型，在心室肌细胞产生动作电位。这些模型将提供深入了解这些通道在健康和疾病状态下的动作电位产生中的作用。此外，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。