Effects of female steroid hormones on A-type K+ currents in murine colon
Effects of female steroid hormones on A-type K+ currents in murine colon
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DOI：
10.1113/jphysiol.2006.107375
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发表时间：
2006-06-01
影响因子：
5.5
通讯作者：
Koh, Sang Don
中科院分区：
文献类型：
--
作者：
Beckett, Elizabeth A. H.;McCloskey, Conor;Koh, Sang Don
育龄妇女的特发性便秘发生率高于绝经后妇女或男性，提示女性类固醇激素影响胃肠运动。女性荷尔蒙如何影响运动尚不清楚。结肠运动受结肠肌细胞离子通道的调控。电压依赖性K+通道可调节结肠肌肉的兴奋性。我们研究了Kv4.3通道表达对女性激素急性或慢性变化的响应。采用膜片潮湿实验和定量PCR方法比较雄性、未妊娠、妊娠和去卵巢小鼠结肠肌细胞的外向电流和转录本表达。切除卵巢的小鼠组接受雌激素或黄体酮注射，以研究激素替代的效果。未怀孕雌鼠结肠肌细胞容量大于雄鼠。雄性和去卵巢小鼠的净外向电流密度高于未怀孕的雌性和经雌激素处理的去卵巢小鼠。妊娠后期的当前密度低于女性对照。黄体酮对向外电流没有影响。与去卵巢小鼠相比，未怀孕的雌性小鼠的a型电流降低，并且通过怀孕或雌激素替代进一步降低。Kv4.3转录本组间差异不显著；然而，与雌性对照组和经雌激素处理的去卵巢小鼠相比，去卵巢小鼠中钾通道相互作用蛋白KChIP1的表达升高。延迟整流电流不受雌激素的影响。在小鼠结肠中，雌激素抑制a型电流，这对调节兴奋性很重要。这些观察结果表明，女性荷尔蒙与月经、怀孕和更年期相关的结肠运动改变之间可能存在联系。
Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K+ channels serve to set the excitability of colonic muscles. We investigated regulation of Kv4.3 channel expression in response to acute or chronic changes in female hormones. Patch damp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause.