Biophysics of Cardiac Rhythms

这项建议涉及研究的三个主要方面， 阐明了心脏节律的机制：（1）单 通道门控机制，（2）重构心脏活动 潜力，以及药理学药物对 动作电位的传播。 一般的做法是 数学建模和相关的模型与 实验数据来源于生理学研究， 他人 具体而言，本建议的第一部分涉及 心脏细胞中离子通道活性的观点， 非马尔可夫威布尔动力学 马尔可夫模型将 与非马尔可夫模型进行比较，以确定其相对 优点，并确定是否非马尔可夫威布尔模型 可以归类为"分形"模型。 的第二部分 一个建议涉及建设一个最低限度的统一模式 心脏动作电位的实验数据 电流由他人获得，以便研究的动态作用， 自发搏动下的区室化钙离子 条件下，并构建一个数学模型，为心脏 动作电位 本建议的第三部分涉及 说明钙通道阻滞剂对 动作电位传播 为了实现这些目标， 心脏脉冲的启动和传播将使用 Cray X-MP/48超级计算机，研究离子 信道特性将改变传播的特性， 波 先进的科学计算机的可用性极大地 扩大了使用数学建模作为 研究生理过程的方法。 虽然模型的 心脏动作电位已经被关注了很多年， 实验的进展提供了新的信息， 被纳入到更复杂的模型中，反过来， 可能指向更精细的实验。 的最终目标 这些方法是为了全面了解 电现象的节奏活动的基础， 心

This proposal addresses three major aspects of research to elucidate the mechanisms underlying cardiac rhythms: (1) single channel gating mechanisms, (2) reconstructing caridac action potentials, and three effects of pharmacological agents on the propagation of action potentials. The general approach is mathematical modeling and correlation of the models with experimental data derived from the physiological studies of others. Specifically, the first part of this proposal deals with the ionic channel activity in heart cells from the viewpoint of non-Markovian Weibull kinetics. Markovian models will be compared with non-Markovian models to determine their relative merits and to determine whether the non-Markovian Weibull model can be classified as a "fractal" model. The second part of the proposal deals with the construction of a minimal unified model for cardiac action potentials using experimental data on action currents obtained by others, so as to study the dynamic role of compartmentalized calcium ions under spontaneous beating conditions, and to construct a mathematical model for the cardiac action potential. The third part of this proposal deals with elucidation of the effect of calcium channel blockers on the action potential propagation. To acheive these objectives the cardiac impulse initiation and propagation will be simulated using the Cray X-MP/48 supercomputer and study how changes in the ionic channel properties would alter the properties of the propagating waves. The availability of advanced scientific computers has greatly expanded the possibility for using mathematical modeling as an approach to study physiological processes. Although models of the heart action potential have been of interest for many years, experimental advances have provided new information that can now be incorporated into more sophisticated models which, in turn, may point to more refined experiments. The ultimate goal of these approaches is to develop a thorough understanding of the electrical phenomena that underly the rythmic activity of the heart.