Ablation of Cav2.3 / E–type voltage–gated calcium channel results in cardiac arrhythmia and altered autonomic control within the murine cardiovascular system

Ablation of Cav2.3 / E–type voltage–gated calcium channel results in cardiac arrhythmia and altered autonomic control within the murine cardiovascular system
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Cav2.3 / E型电压门控的消融

DOI:
10.1007/s00395-004-0488-1
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发表时间:
2004
影响因子:
9.5
通讯作者:
T. Schneider
T. Schneider
中科院分区:
医学1区
文献类型:
--
作者:
M. Weiergräber;M. Henry;M. Südkamp;E. Vivie;J. Hescheler;T. Schneider

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电压门控性钙通道是心肌细胞的重要组成部分, 电生理学我们证明Cav2.3在小鼠中表达, 人心脏和缺乏Cav2.3电压门控钙通道小鼠 心脏功能出现严重改变扩增的cDNA片段 从小鼠心脏和单个心肌细胞的表达揭示了三个 不同的Cav2.3剪接变体。发现Cav2.3的消融伴随有 通过Cav3.1 T型钙通道的补偿性上调, 而其它电压门控钙通道不受影响。遥测 Cav2.3缺陷小鼠的ECG记录显示辅助性 逸搏节律,心房激动模式改变,房室传导 QRS-形态的紊乱和改变。此外,时域 Cav2.3(-)心率变异性(HRV)分析|- )小鼠表现出心率以及变异系数(CV)的显著增加 与对照组小鼠相比。阿托品/普萘洛尔给药显示 心率加快是由于交感神经紧张增强, Cav2.3(-)中CV降低|- )自主神经阻滞后的小鼠 完全消除了二度房室传导阻滞然而,在这方面, 逸搏节律、心房激动紊乱和QRS-畸形 保持不受影响,表明这些是内在的心脏功能, Cav2.3(-|- )小鼠。我们的结论是Cav2.3的表达对于 小鼠心脏的正常脉冲产生和传导。
AbstractVoltage–gated calcium channels are key components in cardiac electrophysiology. We demonstrate that Cav2.3 is expressed in mouse and human heart and that mice lacking the Cav2.3 voltage–gated calcium channel exhibit severe alterations in cardiac function. Amplified cDNA fragments from murine heart and single cardiomyocytes reveal the expression of three different Cav2.3 splice variants. The ablation of Cav2.3 was found to be accompanied by a compensatory upregulation of the Cav3.1 T–type calcium channel, while other voltage–gated calcium channels remained unaffected. Telemetric ECG recordings from Cav2.3 deficient mice displayed subsidiary escape rhythm, altered atrial activation patterns, atrioventricular conduction disturbances and alteration in QRS–morphology. Furthermore, time domain analysis of heart rate variability (HRV) in Cav2.3(–|–) mice exhibited a significant increase in heart rate as well as in the coefficient of variance (CV) compared to control mice. Administration of atropin/propranolol revealed that increased heart rate was due to enhanced sympathetic tonus and that partial decrease of CV in Cav2.3(–|–) mice after autonomic block was in accordance with a complete abolishment of 2nd degree atrioventricular block. However, escape rhythms, atrial activation disturbances and QRS–dysmorphology remained unaffected, indicating that these are intrinsic cardiac features in Cav2.3(–|–) mice. We conclude that the expression of Cav2.3 is essential for normal impulse generation and conduction in murine heart.
胚胎干细胞来源的心肌细胞中 T 型 Ca2 通道的表征和调节。
DOI: 10.1152/ajpheart.01114.2002
发表时间: 2003
期刊: American journal of physiology. Heart and circulatory physiology
影响因子: --
作者:
Zhang,YingMing;Shang,Lijuan;Hartzell,Criss;Narlow,Michael;Cribbs,Leanne;DudleyJr,SamuelC
通讯作者: DudleyJr,SamuelC
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发表时间: 1997
影响因子: 11.1
作者:
Piedras-Rentería,ES;Chen,CC;Best,PM
通讯作者: Best,PM
DOI: 10.1152/jn.1997.78.3.1476
发表时间: 1997-09-01
影响因子: 2.5
作者:
Jeong, SW;Wurster, RD
通讯作者: Wurster, RD
DOI: 10.1152/ajpheart.2000.279.2.h733
发表时间: 2000-08-01
影响因子: 4.8
作者:
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通讯作者: Berul, CI