Functional embryonic cardiomyocytes after disruption of the L-type α1C (Cav1.2) calcium channel gene in the mouse
Functional embryonic cardiomyocytes after disruption of the L-type α1C (Cav1.2) calcium channel gene in the mouse
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DOI：
10.1074/jbc.m006467200
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发表时间：
2000-12-15
影响因子：
4.8
通讯作者：
Hofmann, F
中科院分区：
文献类型：
--
作者：
Seisenberger, C;Specht, V;Hofmann, F
L型α（1c）（Ca（V）1.2）钙通道是心肌和平滑肌中的主要钙进入途径。我们在两个独立的小鼠品系中灭活了Ca（nu）1.2基因，这两个品系具有不可区分的表型。纯合子敲除胚胎（Ca（V）1.2-/-）在交配后（p.c.）14.5天前死亡，在交配后第12.5天，在野生型（+/+）、杂合型（+/-）和纯合型（-/-）Ca（V）1.2胚胎中，胚胎心脏以相同的频率收缩。离体胚胎心肌细胞的搏动依赖于细胞外钙离子，可被1 μ M尼索地平阻断。在（+/+）、（+/-）和（-/-）心肌细胞中，L型Ba ~（2+）内向电流（I-Ba）在所有基因型中都存在，并可被Bay K 8644刺激。在-80 mV的保持电位下，尼索地平阻断了交配后第12.5天的I-Ba。（+/+）和（+/-）细胞，两个IC 50值分别为约0.1和约1 μ M。I-Ba对（-/-）心肌细胞的抑制呈双相性，IC_（50）约为1 μ m。在交配后12.5天，低亲和力I-Ba也存在于α（1D）（Ca（V）1.3）基因敲除的纯合子胚胎的心肌细胞中。这些结果表明，直到交配后第14天，鼠胚胎心脏的收缩需要未鉴定的、低亲和力的L型样钙通道。
The L-type alpha (1c) (Ca(V)1.2) calcium channel is the major calcium entry pathway in cardiac and smooth muscle. We inactivated the Ca(nu)1.2 gene in two independent mouse lines that had indistinguishable phenotypes. Homozygous knockout embryos (Ca(V)1.2-/-) died before day 14.5 postcoitum (p.c.), At day 12.5 p.c., the embryonic heart contracted with identical frequency in wild type (+/+), heterozygous (+/-), and homozygous (-/-) Ca(V)1.2 embryos. Beating of isolated embryonic cardiomyocytes depended on extracellular calcium and was blocked by 1 muM nisoldipine, In (+/+), (+/-), and (-/-) cardiomyocytes, an L-type Ba2+ inward current (I-Ba) was present that was stimulated by Bay K 8644 in all genotypes. At a holding potential of -80 mV, nisoldipine blocked I-Ba of day 12.5 p.c. (+/+) and (+/-) cells with two IC50 values of approximate to0.1 and approximate to1 muM. Inhibition of I-Ba of (-/-) camdiomyocytes was monophasic with an IC50 of approximate to1 mum. The low affinity I-Ba was also present in cardiomyocytes of homozygous alpha (1D) (Ca(V)1.3) knockout embryos at day 12.5 p.c. These results indicate that, up to day 14 p.c., contraction of murine embryonic hearts requires an unidentified, low affinity L-type like calcium channel.