Membrane potential and Ca2+ concentration dependence on pressure and vasoactive agents in arterial smooth muscle: A model.
Membrane potential and Ca2+ concentration dependence on pressure and vasoactive agents in arterial smooth muscle: A model.
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DOI：
10.1085/jgp.201511380
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Karlin A
中科院分区：
文献类型：
--
作者：
Karlin A
一个包含连接和拉伸激活的微域和37个蛋白质组分的数学模型描述了动脉平滑肌细胞的生肌反应。动脉平滑肌(SM)细胞对血管内压的变化做出自主反应，调节张力以保持血管直径。在压力变化的几分钟内，膜电位(Vm)和肌浆钙浓度(CaN)的值是两条相反的通路的结果，这两条通路都使用钙作为信号。这是因为这两条钙信号通路被限制在不同的微域中，在这些微域中，激活关键通道所需的钙离子浓度暂时高于凯恩。提出了一个包含这两种微域的分离的动脉SM细胞的数学模型。第一种类型包括外周肌浆网池和肌膜之间的连接，前者含有兰尼定受体(RyRs)，后者含有电压和钙激活的K+(BK)通道。这些连接微区促进超极化、降低凯恩和松弛。第二种类型被认为是在拉伸激活的非特异性阳离子通道和邻近的钙激活的Cl-−通道周围形成的，并促进相反的(去极化，增加的CaN和收缩)。该模型包括三个额外的隔室：肌浆、中央SR管腔和外围SR管腔。它含有37种蛋白质成分。除压力外，该模型还包括α和β肾上腺素能激动剂、三磷酸腺苷、11，12-环氧二十碳三烯酸和一氧化氮(NO)的输入。对方程的参数进行了调整，以获得与已在脑动脉中确定的Vm和Cain作为压力函数的报告的紧密拟合。模拟对大多数参数的±10%变化不敏感。该模型还模拟了抑制RyR、BK或电压激活的钙通道对Vm和Cain的影响。已知BKβ1亚基缺失会增加动脉-SM张力。在该模型中，在所有压力下，β-1基因的缺失提高了CaN，而这些增加被NO逆转。
A mathematical model incorporating junctional and stretch-activated microdomains and 37 protein components describes the myogenic response in arterial smooth muscle cells. Arterial smooth muscle (SM) cells respond autonomously to changes in intravascular pressure, adjusting tension to maintain vessel diameter. The values of membrane potential (Vm) and sarcoplasmic Ca2+ concentration (Cain) within minutes of a change in pressure are the results of two opposing pathways, both of which use Ca2+ as a signal. This works because the two Ca2+-signaling pathways are confined to distinct microdomains in which the Ca2+ concentrations needed to activate key channels are transiently higher than Cain. A mathematical model of an isolated arterial SM cell is presented that incorporates the two types of microdomains. The first type consists of junctions between cisternae of the peripheral sarcoplasmic reticulum (SR), containing ryanodine receptors (RyRs), and the sarcolemma, containing voltage- and Ca2+-activated K+ (BK) channels. These junctional microdomains promote hyperpolarization, reduced Cain, and relaxation. The second type is postulated to form around stretch-activated nonspecific cation channels and neighboring Ca2+-activated Cl− channels, and promotes the opposite (depolarization, increased Cain, and contraction). The model includes three additional compartments: the sarcoplasm, the central SR lumen, and the peripheral SR lumen. It incorporates 37 protein components. In addition to pressure, the model accommodates inputs of α- and β-adrenergic agonists, ATP, 11,12-epoxyeicosatrienoic acid, and nitric oxide (NO). The parameters of the equations were adjusted to obtain a close fit to reported Vm and Cain as functions of pressure, which have been determined in cerebral arteries. The simulations were insensitive to ±10% changes in most of the parameters. The model also simulated the effects of inhibiting RyR, BK, or voltage-activated Ca2+ channels on Vm and Cain. Deletion of BK β1 subunits is known to increase arterial–SM tension. In the model, deletion of β1 raised Cain at all pressures, and these increases were reversed by NO.
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影响因子：
64.8
作者：
Alon, U;Surette, MG;Leibler, S
通讯作者：
Leibler, S
DOI：
10.1152/ajpheart.01286.2006
发表时间：
2007-06-01
影响因子：
4.8
作者：
Earley, Scott;Straub, Stephen V.;Brayden, Joseph E.
通讯作者：
Brayden, Joseph E.
影响因子：
4.8
作者：
Dessauer, CW;Gilman, AG
通讯作者：
Gilman, AG
影响因子：
20.1
作者：
Adebiyi A;Zhao G;Narayanan D;Thomas-Gatewood CM;Bannister JP;Jaggar JH
通讯作者：
Jaggar JH
影响因子：
4.8
作者：
Aziz, Qadeer;Thomas, Alison M.;Tinker, Andrew
通讯作者：
Tinker, Andrew