Lu Zhong-Ju, Pereverzev Alexey, Liu Hui-Lin, Weiergräber Marco, Henry Margit, Krieger Andreas, Smyth Neil, Hescheler Jürgen, Schneider Toni
Institute of Neurophysiology, Medical Faculty, University of Köln, Germany.
Cell Physiol Biochem. 2004;14(1-2):11-22. doi: 10.1159/000076922.
A voltage-gated calcium channel containing Cav2.3e (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 Cav1.2 had been ablated. The remaining "L-type like" current component was not related to recombinant splice variants of Cav1.3 containing channels. As recombinant Cav2.3 channels from rat were reported to be weakly dihydropyridine sensitive, the spontaneous activity of the prenatal hearts from Cav2.3(-|-) mice was compared to that of Cav2.3(+|+) control animals to investigate if Cav2.3 could represent such a L-type like Ca(2+) 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 Cav2.3-deficient mice did not differ significantly from control mice but the coefficient of variation within individual episodes was more than four-fold increased in Cav2.3-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 Cav2.3e as ion conducting pore stabilize a more regular heart beat in prenatal mice.
最近在大鼠心脏中检测到一种以Cav2.3e（α1Ee）作为离子传导孔的电压门控钙通道。除了L型和T型通道外，该钙通道参与心脏跳动调节的功能证据来自Cav1.2基因被敲除的小鼠胚胎。剩余的“类L型”电流成分与含有Cav1.3通道的重组剪接变体无关。由于据报道大鼠的重组Cav2.3通道对二氢吡啶的敏感性较弱，因此将Cav2.3（-/-）小鼠产前心脏的自发活动与Cav2.3（+/+）对照动物的进行比较，以研究Cav2.3是否可能代表这样一种类L型钙通道。使用多电极阵列记录小鼠胚胎心脏的自发活动。在妊娠第9.5天至12.5天期间，Cav2.3缺陷小鼠分离胚胎心脏的跳动频率与对照小鼠相比无显著差异，但Cav2.3缺陷小鼠个体发作内的变异系数增加了四倍多，表明存在心律失常。在野生型小鼠的分离心脏中，用含有200 nM SNX-482（一种某些R型电压门控钙通道的阻滞剂）的溶液灌注可诱发心律失常，这表明含有剪接变体Cav2.3e作为离子传导孔的R型通道可稳定产前小鼠更规律的心跳。
