GLOBAL PARAMETER OPTIMIZATION FOR CARDIAC POTASSIUM CHANNEL GATING MODELS
GLOBAL PARAMETER OPTIMIZATION FOR CARDIAC POTASSIUM CHANNEL GATING MODELS
复制标题
DOI：
10.1016/s0006-3495(90)82560-1
复制
发表时间：
1990-03-01
影响因子：
3.4
通讯作者：
BENNETT, PB
中科院分区：
文献类型：
--
作者：
BALSER, JR;RODEN, DM;BENNETT, PB
定量离子通道模型评价需要电压依赖性速率常数的估计。我们已经测试了是否可以可靠地从非平稳宏观电压钳钾电流数据中提取一组独特的速率常数。对于许多模型，在不同的膜电位下独立导出的速率常数不是唯一的。因此，我们的方法是使用从反应速率理论预测的指数电压依赖性（Stevens，C. F. 1978. Biophys. J. 22：295-306; Eyring H.，S. H. Lin和S. M.是林书1980.基础化学动力学Wiley和Sons，纽约）来耦合在不同膜电位下得到的速率常数。这将速率常数的解集约束为仅服从这一附加方程组的那些，这足以获得唯一解。我们已经测试了这种方法与宏观延迟整流钾通道电流在电压钳位豚鼠心室肌细胞膜获得的数据。这种钾通道具有相对简单的动力学，没有失活过程，并提供了一个方便的系统，以确定一组全局优化的电压依赖性速率常数的马尔可夫动力学模型。使用从已知速率常数合成的“数据”测试拟合算法从宏观电流数据提取速率常数的能力。用全局拟合程序分析模拟数据集，并将拟合的速率常数与用于生成数据的速率常数进行比较。用蒙特卡罗方法考察了动力学参数估计的准确性。这种全局拟合方法提供了一个有用的和covenient方法可靠地提取马尔可夫速率常数从宏观电压钳数据在广泛的膜电位。该方法的局限性和依赖于初始猜测进行了说明。
Quantitative ion channel model evaluation requires the estimation of voltage dependent rate constants. We have tested whether a unique set of rate constants can be reliably extracted from nonstationary macroscopic voltage clamp potassium current data. For many models the rate constants derived independently at different membrane potentials are not unique. Therefore, our approach has been to use the exponential voltage dependence predicted from reaction rate theory (Stevens, C. F. 1978. Biophys. J. 22:295-306; Eyring H., S. H. Lin, and S. M. Lin. 1980. Basic Chemical Kinetics. Wiley and Sons, New York) to couple the rate constants derived at different membrane potentials. This constrained the solution set of rate constants to only those that also obeyed this additional set of equations, which was sufficient to obtain a unique solution. We have tested this approach with data obtained from macroscopic delayed rectifier potassium channel currents in voltage-clamped guinea pig ventricular myocyte membranes. This potassium channel has relatively simple kinetics without an inactivation process and provided a convenient system to determine a globally optimized set of voltage-dependent rate constants for a Markov kinetic model. The ability of the fitting algorithm to extract rate constants from the macroscopic current data was tested using "data" synthesized from known rate constants. The simulated data sets were analyzed with the global fitting procedure and the fitted rate constants were compared with the rate constants used to generate the data. Monte Carlo methods were used to examine the accuracy of the estimated kinetic parameters. This global fitting approach provided a useful and covenient method for reliably extracting Markov rate constants from macroscopic voltage clamp data over a broad range of membrane potentials. The limitations of the method and the dependence on initial guesses are described.