Matrine inhibits pacing induced atrial fibrillation by modulating I(KM3) and I(Ca-L).
Matrine inhibits pacing induced atrial fibrillation by modulating I(KM3) and I(Ca-L).
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DOI：
10.7150/ijbs.8.150
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发表时间：
2012
影响因子：
9.2
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Zhou Y;Xu W;Han R;Zhou J;Pan Z;Rong H;Li J;Xu C;Qiao G;Lu Y
目的：探讨苦参碱对电起搏诱发小鼠心房颤动的保护作用及其分子和离子通道机制。方法：采用电起搏的方法建立小鼠房颤模型，观察房颤的发生率和持续时间。用Western和Real-time PCR法检测M3受体(M3-R)和Cav1.2的功能表达，全细胞膜片记录动作电位(AP)和(IKM3)L型钙通道密度(ICa-L)。结果：对照组电起搏诱发房颤的发生率和持续时间分别为50±17%和3.68±1.84 S，应用卡巴胆碱50µg/kg后，房颤的发生率和持续时间均显著增加，分别为86±24%和65.2±29.0 S，与对照组相比，苦参碱预处理15天可显著降低房颤的发生率和持续时间，且呈剂量依赖关系。心房膜M3-R蛋白表达降低，膜Cav1.2表达上调。单用苦参碱处理的心房肌细胞，IkM_3密度较对照组显著降低39%，而ICa-L密度较对照组增加40%。结论：首次证实苦参碱的抗房颤作用可能至少部分是通过下调IkM_3密度和M3-R表达，上调ICa-L密度和α1C/Cav1.2的表达而实现的。
Aim: To elucidate the protective effects of Matrine on atrial fibrillation (AF) induced by electric pacing in mice and underlying molecular and ion channel mechanisms. Methods: AF was introduced by electric pacing in mice and the incidence and duration of AF were evaluated. Functional expression of M3 receptor (M3-R) and Cav1.2 were explored by western and Real-time PCR, action potential (AP) and the density of (IKM3) L-type calcium channel (ICa-L) were both recorded using whole-cell patch in isolated atrial cardiomyocytes. Results: In control group, incidence and duration of AF induced by electric pacing were 50 ± 17% and 3.68 ± 1.84 s, respectively; after application of carbachol 50 µg/kg both incidence and duration of AF were significantly increased to 86 ± 24% and 65.2 ± 29.0 s. Compared with control group, pretreatment of Matrine for 15 days significantly reduced AF incidence and duration in dose-dependent manner. Atrial membrane-protein expression of M3-R was decreased and membrane Cav1.2 expression was up-regulated. In single Matrine-treated atrial cardiomyocyte the density of IKM3 was significantly decreased by 39% as well compared with control group, P < 0.05, whereas, ICa-L density of atrium was increased by 40%. Conclusion: These data demonstrated at the first time that the anti-AF effects of Matrine may due, at least in part, to down-regulation of IKM3 density and M3-R expression and up-regulation of ICa-L density and α1C/Cav1.2 expression.
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影响因子：
39.3
作者：
Pedersen, OD;Abildstrom, SZ;Torp-Pedersen, C
通讯作者：
Torp-Pedersen, C
影响因子：
10.8
作者：
Fareh, S;Bénardeau, A;Nattel, S
通讯作者：
Nattel, S
影响因子：
20.1
作者：
SCHUESSLER, RB;ROSENSHTRAUKH, LV;COX, JL
通讯作者：
COX, JL
影响因子：
37.8
作者：
MORILLO, CA;KLEIN, GJ;GUIRAUDON, CM
通讯作者：
GUIRAUDON, CM
影响因子：
37.8
作者：
Berul, CI;Aronovitz, MJ;Mendelsohn, ME
通讯作者：
Mendelsohn, ME