Walton M, Fozzard H A
Biophys J. 1979 Mar;25(3):407-20. doi: 10.1016/S0006-3495(79)85312-6.
The inward sodium current in cardiac muscle is difficult to study by voltage clamp methods, so various indirect experimental measures have been used to obtain insight into its characteristics. These methods depend on the relationship between maximal upstroke velocity of the action potential (Vmax) and the sodium current (INa), usually defined in terms of the Hodgkin-Huxley model. These relationships were explored using an adaptation of this model to cardiac Purkinje fibers. In general Vmax corresponded to INa, and it could be used to determine the relationship of membrane potential to GNa, and h infinity. The results, however, depended on the method of stimulation of the action potential, and an optimal stimulation method was determined. A commonly used experimental technique called "membrane responsiveness" was shown to distort seriously the properties of steady-state gating inactivation that is supposed to measure. Estimation of the changes in maximal sodium conductance, such as those produced by tetrodotoxin (TTX), would be accurately measured. Some experimental results have indicated a voltage-dependent effect of TTX. Characteristics of the measures of TTX effect under those conditions were illustrated. In summary, calculations with a model of the cardiac Purkinje fiber action potential provide insight into the accuracy of certain experimental methods using maximal upstroke velocity as a measure of INa, and cast doubt on other experimental methods, such as membrane responsiveness.
心肌中的内向钠电流很难通过电压钳方法进行研究，因此人们采用了各种间接实验措施来深入了解其特性。这些方法依赖于动作电位的最大上升速度（Vmax）与钠电流（INa）之间的关系，通常是根据霍奇金 - 赫胥黎模型来定义的。利用该模型对心脏浦肯野纤维的一种改编形式来探究这些关系。一般来说，Vmax与INa相对应，并且它可用于确定膜电位与GNa以及h无穷大之间的关系。然而，结果取决于动作电位的刺激方法，并且确定了一种最佳刺激方法。一种常用的实验技术，即所谓的“膜反应性”，被证明会严重扭曲其本应测量的稳态门控失活特性。最大钠电导变化的估计，例如由河豚毒素（TTX）产生的变化，将被准确测量。一些实验结果表明了TTX的电压依赖性效应。阐述了在那些条件下TTX效应测量的特点。总之，用心脏浦肯野纤维动作电位模型进行的计算，有助于深入了解某些以最大上升速度作为INa测量指标的实验方法的准确性，并对其他实验方法，如膜反应性，产生怀疑。
