Slow ventricular conduction in mice heterozygous for a connexin43 null mutation
Slow ventricular conduction in mice heterozygous for a connexin43 null mutation
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DOI：
10.1172/jci119367
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发表时间：
1997-04-15
影响因子：
15.9
通讯作者：
Saffitz, JE
中科院分区：
文献类型：
--
作者：
Guerrero, PA;Schuessler, RB;Saffitz, JE
为了表征差距连接蛋白连接蛋白43（Cx43）在心室传导中的作用，我们研究了Cx43基因靶向缺失的小鼠心脏。Cx43无效突变（CX43-/-）纯合小鼠出生后不久就死亡。尝试记录新生儿Cx43-/-心脏（n = 5）的电活动不成功。然而，杂合子（Cx43-/+）新生儿心脏起搏搏动的心室心外膜传导（0.14 +/-0.04 m/s，n = 27）比野生型（Cx43 +/+）心脏（0.20 +/-0.07 m/s，n = 32; P <0.001）慢30%。这种表型在成年小鼠中甚至更严重; 6 - 9月龄Cx43-/+心脏的心室心外膜传导（0.18 +/-0.03 m/s，n = 5）比野生型心脏（0.32 +/-0.07 m/s，n = 7，P <0.001）慢44%。心电图显示成年Cx43-/+小鼠的QRS波群（13.4 ± 1.8 ms，n = 13）较Cx43 +/+小鼠（11.5 ± 1.4 ms，n = 12，P <0.01）明显延长。培养的新生儿心室肌细胞从Cx43-/+和+/+心脏的动作电位参数的全细胞记录显示没有差异。因此，通过靶向缺失Cx43等位基因减少主要心脏间隙连接蛋白的丰度直接导致心室传导减慢。
To characterize the role of the gap junction protein connexin43 (Cx43) in ventricular conduction we studied hearts of mice with targeted deletion of the Cx43 gene. Mice homozygous for the Cx43 null mutation (CX43 -/-) die shortly after birth. Attempts to record electrical activity in neonatal Cx43 -/- hearts (n = 5) were unsuccessful. Ventricular epicardial conduction of paced beats, however, was 30% slower in heterozygous (Cx43 -/+) neonatal hearts (0.14+/-0.04 m/s, n = 27) than in wild-type (Cx43 +/+) hearts (0.20+/-0.07 m/s, n = 32; P < 0.001). This phenotype was even more severe in adult mice; ventricular epicardial conduction was 44% slower in 6-9 mo-old Cx43 -/+ hearts (0.18+/-0.03 m/s, n = 5) than in wild-type hearts (0.32+/-0.07 m/s, n = 7, P < 0.001). Electrocardiograms revealed significant prolongation of the QRS complex in adult Cx43 -/+ mice (13.4+/-1.8 ms, n = 13) compared with Cx43 +/+ mice (11.5+/-1.4 ms, n = 12, P < 0.01). Whole-cell recordings of action potential parameters in cultured disaggregated neonatal ventricular myocytes from Cx43 -/+ and +/+ hearts showed no differences. Thus, reduction in the abundance of a major cardiac gap junction protein through targeted deletion of a Cx43 allele directly leads to slowed ventricular conduction.