Castellanos P, Godinez R
Annu Int Conf IEEE Eng Med Biol Soc. 2015;2015:43-6. doi: 10.1109/EMBC.2015.7318296.
In the last years different computational models have been proposed to simulate the sinoatrial node cell (SANC) action potential. Also, there has been a great effort to model the heart regulation mechanism by the autonomic nervous system (ANS) through the sympathetic and parasympathetic pathways. Both computational models have tried to fit the rabbit and/or the guinea-pig experimental heart rate data with an increasing success. Thus, the aim of this work was to unify the available models that have been reported to study the heart rate behavior when the SANC is stimulated by using different frequency patterns. Our results contribute to the unification of part of the Scepanovic's model [1] (involved with second messengers dynamics and its influence over specific SANC ionic channels), and the SANC ionic channels computational model proposed by Severi et al. [2] in 2012. In this model unification we did refit some parameters, particularly, those related to the Hill functions in the dynamic modeling of phosphokinase and its effect on the ionic channels currents If and ICaL, and over the Pup, parameter that is related to the Ca(++) uptake by the sarcoplasmic reticulum. Also, we eliminated the neurotransmitter effect over the ionic current IKr that is not presented in the Severi's model. These modifications were enough to successfully reproduce the heart rate experimental recordings under acetylcholine (Ach) or norepinephrine (NE) for independent stimulation: Ach 10 nM stimulation showed a 21.54% action potential shift compared with the 20% reported for experimental recordings; Isoprenaline 1 μM, also displayed a depolarization increased rate of 29.3%, compared with the experimental data of 28.2%. Furthermore, we were able to reproduce the guinea-pig experimental heart rate recordings, when the SANC model was vagal stimulated by using a 2 Hz, 10 Hz and 20 Hz frequency for 10 seconds and the experimental heart rate data for a sympathetic stimulation of 10 Hz frequency for 10 seconds.
在过去几年中，已经提出了不同的计算模型来模拟窦房结细胞（SANC）动作电位。此外，人们还付出了巨大努力，通过交感神经和副交感神经途径，对自主神经系统（ANS）调节心脏的机制进行建模。这两种计算模型都在尝试拟合兔子和/或豚鼠的实验心率数据，并且越来越成功。因此，这项工作的目的是统一已报道的可用模型，这些模型用于研究当SANC受到不同频率模式刺激时的心率行为。我们的结果有助于将Scepanovic模型[1]（涉及第二信使动力学及其对特定SANC离子通道的影响）的一部分，与Severi等人在2012年提出的SANC离子通道计算模型[2]进行统一。在这个模型统一过程中，我们重新调整了一些参数，特别是那些与磷酸激酶动态建模中的希尔函数相关的参数，以及它对离子通道电流If和ICaL的影响，还有与肌浆网对Ca(++)摄取相关的Pup参数。此外，我们消除了神经递质对离子电流IKr的影响，因为Severi模型中没有这一影响。这些修改足以成功再现乙酰胆碱（Ach）或去甲肾上腺素（NE）独立刺激下的心率实验记录：1 nM Ach刺激显示动作电位偏移21.5%，而实验记录报道为20%；1 μM异丙肾上腺素也显示去极化速率增加29.3%，而实验数据为28.2%。此外，当SANC模型分别以2 Hz、10 Hz和20 Hz频率进行10秒的迷走神经刺激，以及以10 Hz频率进行10秒的交感神经刺激时，我们能够再现豚鼠的实验心率记录。
