Mechanistic Insights Into the Reduced Pacemaking Rate of the Rabbit Sinoatrial Node During Postnatal Development: A Simulation Study.
Mechanistic Insights Into the Reduced Pacemaking Rate of the Rabbit Sinoatrial Node During Postnatal Development: A Simulation Study.
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DOI：
10.3389/fphys.2020.547577
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发表时间：
2020
影响因子：
4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Alghamdi AM;Testrow CP;Whittaker DG;Boyett MR;Hancox JC;Zhang H
新生和成人窦房结细胞的形态和动作电位（AP）特征存在明显的年龄和发育差异。这些可能是由于不同年龄之间的一组不同的离子通道相互作用。然而，根本的机制尚未阐明。本研究的目的是通过生物物理模拟方法确定新生和成年家兔心脏SAN细胞之间不同的自发AP和心率的机制。根据从新生兔SAN细胞获得的实验数据，通过修改成年细胞模型中离子通道和转运蛋白的电流密度和/或动力学，开发了新生兔SAN细胞的数学模型。然后将单细胞模型并入完整SAN心房的多细胞二维模型中，以研究成熟过程中改变的离子通道对起搏电活动及其在组织水平上的传导的功能影响。神经递质乙酰胆碱对新生细胞起搏活动的影响也进行了研究，并与成人进行了比较。我们的结果显示：（1）新生儿和成人SAN细胞之间离子通道特性的差异能够解释其AP和心率的差异，为了解出生后发育期间兔窦房结起搏率降低提供了机制见解;（2）在完整SAN心房的2D模型中，研究表明，出生后发育期间的细胞变化通过增加激活时间和降低通过SAN的传导速度而损害起搏活动;（3）新生儿SAN模型搏动频率快，对乙酰胆碱引起的副交感神经调节的敏感性高于成人模型。这些结果为理解新生儿和成人SAN心脏起搏活动差异的细胞机制提供了新的见解。
Marked age- and development- related differences have been observed in morphology and characteristics of action potentials (AP) of neonatal and adult sinoatrial node (SAN) cells. These may be attributable to a different set of ion channel interactions between the different ages. However, the underlying mechanism(s) have yet to be elucidated. The objective of this study was to determine the mechanisms underlying different spontaneous APs and heart rate between neonatal and adult SAN cells of the rabbit heart by biophysical modeling approaches. A mathematical model of neonatal rabbit SAN cells was developed by modifying the current densities and/or kinetics of ion channels and transporters in an adult cell model based on available experimental data obtained from neonatal SAN cells. The single cell models were then incorporated into a multi-cellular, two-dimensional model of the intact SAN-atrium to investigate the functional impact of altered ion channels during maturation on pacemaking electrical activities and their conduction at the tissue level. Effects of the neurotransmitter acetylcholine on the pacemaking activities in neonatal cells were also investigated and compared to those in the adult. Our results showed: (1) the differences in ion channel properties between neonatal and adult SAN cells are able to account for differences in their APs and the heart rate, providing mechanistic insight into understanding the reduced pacemaking rate of the rabbit sinoatrial node during postnatal development; (2) in the 2D model of the intact SAN-atria, it was shown that cellular changes during postnatal development impaired pacemaking activity through increasing the activation time and reducing the conduction velocity across the SAN; (3) the neonatal SAN model, with its faster beating rates, showed a greater sensitivity to parasympathetic modulation in response to acetylcholine than did the adult model. These results provide novel insights into the understanding of the cellular mechanisms underlying the differences in the cardiac pacemaking activities of the neonatal and adult SAN.
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DOI：
10.1196/annals.1380.014
发表时间：
2006-01-01
期刊：
INTERACTIVE AND INTEGRATIVE CARDIOLOGY
影响因子：
--
作者：
Janowski, Einsley;Cleemann, Lars;Morad, Martin
通讯作者：
Morad, Martin
DOI：
10.1159/000092569
发表时间：
2006-01-01
期刊：
CARDIOVASCULAR GAP JUNCTIONS
影响因子：
--
作者：
Boyett, M. R.;Inada, S.;Dobrzynski, H.
通讯作者：
Dobrzynski, H.
影响因子：
5.5
作者：
Honjo, H;Boyett, MR;Toyama, J
通讯作者：
Toyama, J
影响因子：
37.8
作者：
Jones, Sandra A.;Boyett, Mark R.;Lancaster, Matthew K.
通讯作者：
Lancaster, Matthew K.
影响因子：
20.1
作者：
Butters TD;Aslanidi OV;Inada S;Boyett MR;Hancox JC;Lei M;Zhang H
通讯作者：
Zhang H