Arrhythmia in isolated prenatal hearts after ablation of the Cav2.3 (α1E) subunit of voltage-gated Ca2+ channels
Arrhythmia in isolated prenatal hearts after ablation of the Cav2.3 (α1E) subunit of voltage-gated Ca2+ channels
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DOI：
10.1159/000076922
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发表时间：
2004-01-01
影响因子：
--
通讯作者：
Schneider, T
中科院分区：
文献类型：
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作者：
Lu, ZJ;Pereverzev, A;Schneider, T
最近在大鼠心脏中发现了一种含有Ca（v）2.3e（α 1 Ee）作为离子传导孔的电压门控钙通道。除了L-和T-型通道外，这种Ca 2+通道参与心脏跳动调节的功能证据来自小鼠胚胎，其中Ca（v）1.2的基因已被消融。剩余的L型样电流成分与含有Ca（v）1.3通道的重组剪接变体无关。由于来自大鼠的重组Ca（v）2.3通道被报道为弱二氢吡啶敏感的，因此比较了来自Ca（v）2.3（-\-）小鼠和Ca（v）2.3（+\+）对照动物的产前心脏的自发活动，以研究Ca（v）2.3是否可以代表这样的L型样Ca 2+通道。用多电极阵列记录小鼠胚胎心脏的自发活动。第9.5天p.c.至12.5 p.c.，来自Ca（v）2.3-缺陷小鼠的分离的胚胎心脏的搏动频率与对照小鼠没有显著差异，但是在Ca（v）2.3-缺陷小鼠中，单个事件内的变异系数增加了4倍以上，表明心律失常。在来自野生型小鼠的离体心脏中，通过用含有200 nM SNX-482（一些R型电压门控Ca 2+通道的阻断剂）的溶液灌注诱导心律失常，这表明含有剪接变体Ca（v）2.3e作为离子传导孔的R型通道稳定产前小鼠中更规律的心跳。版权所有（C）2004 S. Karger AG，巴塞尔。
A voltage-gated calcium channel containing Ca(v)2.3e (alpha1Ee) as the ion conducting pore has recently been detected in rat heart. Functional evidence for this Ca2+ channel to be involved in the regulation of heart beating, besides L- and T-type channels, was derived from murine embryos where the gene for Ca(v)1.2 had been ablated. The remaining,L-type like" current component was not related to recombinant splice variants of Ca(v)1.3 containing channels. As recombinant Ca(v)2.3 channels from rat were reported to be weakly dihydropyridine sensitive, the spontaneous activity of the prenatal hearts from Ca(v)2.3(-\-) mice was compared to that of Ca(v)2.3(+\+) control animals to investigate if Ca(v)2.3 could represent such a L-type like Ca2+ channel. The spontaneous activity of murine embryonic hearts was recorded by using a multielectrode array. Between day 9.5 p.c. to 12.5 p.c., the beating frequency of isolated embryonic hearts from Ca(v)2.3-deficient mice did not differ significantly from control mice but the coefficient of variation within individual episodes was more than four-fold increased in Ca(v)2.3-deficient mice indicating arrhythmia. In isolated hearts from wild type mice, arrhythmia was induced by superfusion with a solution containing 200 nM SNX-482, a blocker of some R-type voltage gated Ca2+ channels, suggesting that R-type channels containing the splice variant Ca(v)2.3e as ion conducting pore stabilize a more regular heart beat in prenatal mice. Copyright (C) 2004 S. Karger AG, Basel.