Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3
Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3
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DOI：
10.1126/science.289.5486.1942
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发表时间：
2000-09-15
期刊：
影响因子：
56.9
通讯作者：
Adelman, JP
中科院分区：
文献类型：
--
作者：
Bond, CT;Sprengel, R;Adelman, JP
在可兴奋细胞中，小电导 Ca2+ 激活钾通道（SK 通道）导致动作电位后缓慢的后超极化。三个 SK 通道亚基已得到分子特征。通过同源重组将 SK3 基因作为目标，插入一个基因开关，允许对 SK3 表达进行实验调节，同时保留正常的 SK3 启动子功能。 SK3 的缺失不会表现出明显的表型后果。然而，SK3 过度表达会引起缺氧的异常呼吸反应和分娩困难。这两种情况都可以通过沉默基因来纠正。结果表明 SK3 通道是睡眠呼吸暂停或婴儿猝死综合症等疾病以及调节分娩过程中子宫收缩的潜在治疗靶点。
In:excitable cells, small-conductance Ca2+-activated potassium channels (SK channels) are responsible for the slow after-hyperpolarization that often follows an action potential. Three SK channel subunits have been molecularly characterized. The SK3 gene was targeted by homologous recombination for the insertion of a gene switch that permitted experimental regulation of SK3 expression while retaining normal SK3 promoter function. An absence of SK3 did not-present overt phenotypic consequences. However, SK3 overexpression induced abnormal respiratory responses to hypoxia and compromised parturition. Both conditions were corrected by silencing the gene. The results implicate SK3 channels as potential therapeutic targets for disorders such as sleep apnea Or sudden infant death syndrome and for regulating uterine contractions during labor.