Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis
Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis
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DOI：
10.1006/jmcc.2000.1232
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发表时间：
2000-11-01
影响因子：
5
通讯作者：
Pegg, AE
中科院分区：
文献类型：
--
作者：
Lopatin, AN;Shantz, LM;Pegg, AE
心脏I-K1通道的内向整流是通过自然产生的多胺的遗传操纵来调节的。鸟氨酸脱羧酶（ODC）在小鼠心脏α -肌球蛋白重链启动子（α MHC）中心下过表达。在ODC转基因心脏中，腐胺和尸胺的水平高度升高（腐胺类似于35倍），亚精胺增加3.6倍，但精胺基本不变。尽管整流的电压依赖性基本不变，但I-K1密度降低了38%。有趣的是，瞬态向外电流（I-to,I-f）的快速分量增加，但总向外电流幅值不变。在精胺合酶基因被破坏导致精胺完全丧失的突变型Gyro （Gy）小鼠的肌细胞中，也研究了I-K1和I-to电流。在Gy肌细胞中，I-K1电流密度没有改变，但整流的陡峭度降低，表明精胺在控制整流中的作用。用腐胺、亚精胺和精胺对肌细胞进行细胞内透析，分别导致整流度降低、无变化和陡度增加。结合I-K1激活的动力学分析，这些结果与以下观点一致：精胺在E-K电位为正时是主要的整流因子，在E-K电位为负时占主导地位，而腐胺在小鼠心脏整流中没有显著作用。(C) 2000年学术出版社。
Inward rectification of cardiac I-K1 channels was modulated by genetic manipulation of the naturally occurring polyamines. Ornithine decarboxylase (ODC) was overexpressed in mouse heart under central of the cardiac alpha -myosin heavy chain promoter (alpha MHC). In ODC transgenic hearts, putrescine and cadaverine levels were highly elevated (similar to 35-fold for putrescine), spermidine was increased 3.6-fold, but spermine was essentially unchanged. I-K1 density was reduced by similar to 38%, although the voltage-dependence of rectification was essentially unchanged. Interestingly the fast component of transient outward (I-to,I-f) current was increased, but the total outward current amplitude was unchanged. I-K1 and I-to currents were also studied in myocytes from mutant Gyro (Gy) mice in which the spermine synthase gene is disrupted, leading to a complete loss of spermine. I-K1 current densities were not altered in Gy myocytes, but the steepness of rectification was reduced indicating a role for spermine in controlling rectification. Intracellular dialysis of myocytes with putrescine, spermidine and spermine caused reduction, no change and increase of the steepness of rectification, respectively. Taken together with kinetic analysis of I-K1 activation these results are consistent with spermine being a major rectifying factor at potentials positive to E-K, spermidine dominating at potentials around and negative to E-K, and putrescine playing no significant role in rectification in the mouse heart. (C) 2000 Academic Press.