Tanskanen Antti J, Alvarez Luis H R
Institute for Computational Medicine and the Center for Cardiovascular Bioinformatics and Modeling, The Johns Hopkins University School of Medicine and Whiting School of Engineering, Baltimore, MD 21218, USA.
Math Biosci. 2007 Jul;208(1):125-46. doi: 10.1016/j.mbs.2006.09.023. Epub 2006 Oct 25.
Stochastic gating of ion channels introduces noise to membrane currents in cardiac muscle cells (myocytes). Since membrane currents drive membrane potential, noise thereby influences action potential duration (APD) in myocytes. To assess the influence of noise on APD, membrane potential is in this study formulated as a stochastic process known as a diffusion process, which describes both the current-voltage relationship and voltage noise. In this framework, the response of APD voltage noise and the dependence of response on the shape of the current-voltage relationship can be characterized analytically. We find that in response to an increase in noise level, action potential in a canine ventricular myocytes is typically prolonged and that distribution of APDs becomes more skewed towards long APDs, which may lead to an increased frequency of early after-depolarization formation. This is a novel mechanism by which voltage noise may influence APD. The results are in good agreement with those obtained from more biophysically-detailed mathematical models, and increased voltage noise (due to gating noise) may partially underlie an increased incidence of early after-depolarizations in heart failure.
离子通道的随机门控会给心肌细胞(肌细胞)的膜电流引入噪声。由于膜电流驱动膜电位,因此噪声会影响肌细胞的动作电位持续时间(APD)。为了评估噪声对APD的影响,本研究将膜电位表述为一种称为扩散过程的随机过程,该过程描述了电流-电压关系和电压噪声。在此框架下,APD对电压噪声的响应以及响应与电流-电压关系形状的依赖性可以通过解析方法来表征。我们发现,响应于噪声水平的增加,犬心室肌细胞中的动作电位通常会延长,并且APD的分布会更偏向于长APD,这可能会导致早期后去极化形成频率增加。这是电压噪声可能影响APD的一种新机制。这些结果与从生物物理细节更丰富的数学模型中获得的结果高度一致,并且电压噪声增加(由于门控噪声)可能部分是心力衰竭中早期后去极化发生率增加的原因。