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在心房内Cav1.3 ((alpha1D) 通道的功能作用:从基因向的零突变小鼠中获得的见解

Zhao Zhang¹, Yuxia He, Dipika Tuteja

¹Division of Cardiovascular Medicine, University of California, Davis, CA 95616, USA.

|September 21, 2005

概括

卡维1.3通道对正常心律至关重要,主要在心房. 在小鼠中缺少它会导致心房律乱,突出显示它在心脏功能中的重要作用.

科学领域:

心血管生理学心血管生理学
分子心脏病学分子心脏病学
离子通道生物学离子通道生物学

背景情况:

L型Ca2+通道,特别是Cav1.3 (alpha(1D)) 和Cav1.2 (alpha1C) 子单元,具有不同的组织表达.
缺少Cav1.3 Ca2+通道的小鼠 (Cav1.3(-/-)) 呈现出胸和延长的PR间隔.
以前的研究表明,Cav1.3通道主要存在于神经元和神经内分泌细胞中.

研究的目的:

为了研究Cav1.3 (alpha1D) Ca2+通道在Cav1.3的前庭中的作用.
为了确定Cav1.3 Ca2+通道在心房组织中的功能意义.
阐明心脏中Cav1.3与Cav1.2通道的差异分布和功能.

主要方法:

针对基因的删除,以创建Cav1.3 ((-/-) 鼠标.
在孤立的心房和心室肌细胞中,对全细胞L型Ca2+电流 (I(Ca,L)) 的电生理学记录.
在现场杂交和免疫光共聚焦显微镜以确认通道表达.
在Cav1.3的小鼠中诱导心房失常.

主要成果:

与心室组织相比,Cav1.3 Ca2+通道的显著表达主要在心房组织中被发现.
来自Cav1.3(-/-) 小鼠的心房肌细胞显示了I(Ca,L) 的电压依赖激活中的脱极化转移.
Cav1.3-null突变小鼠表现出心房律乱,包括可诱导的心房动和动.
从野生类型和Cav1.3的室腔肌细胞中没有观察到I ((Ca,L) 的显著差异.

结论:

Cav1.3 Ca2+通道分布差异,在心房肌细胞的表达高于心室肌细胞.
这项研究为Cav1.3 Ca2+通道在心房组织中的显著功能作用提供了第一个证据.
缺少Cav1.3通道导致心房电生理学的改变,并促进心律失常.

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