Sexual dimorphism and oestrogen regulation of KCNE3 expression modulates the functional properties of KCNQ1 K+ channels
Sexual dimorphism and oestrogen regulation of KCNE3 expression modulates the functional properties of KCNQ1 K+ channels
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DOI：
10.1113/jphysiol.2011.215772
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发表时间：
2011-11-01
影响因子：
5.5
通讯作者：
Harvey, Brian J.
中科院分区：
文献类型：
--
作者：
Alzamora, Rodrigo;O'Mahony, Fiona;Harvey, Brian J.
KCNQ 1钾通道与各种KCNE辅助亚基相关，这些亚基显著影响通道门控和药理学。与KCNE 3的共组装产生几乎瞬时激活的电流，在非常正的电位下产生一些时间依赖性激活，具有线性电流-电压关系，并且对色原醇293 B的灵敏度高出10倍。KCNQ 1：KCNE 3通道在结肠隐窝中表达，并介导Cl-分泌所需的基底外侧K+再循环。我们以前曾报道雌激素通过抑制结肠隐窝中的KCNQ 1：KCNE 3通道而产生女性特异性的抗分泌作用。本研究旨在探讨性别和雌激素对大鼠远端结肠KCNQ 1和KCNE 3表达和功能的影响。从Sprague-Dawley大鼠分离结肠隐窝，并用于全细胞膜片钳和提取总RNA和蛋白质。使用上皮片进行短路电流记录。KCNE 1和KCNE 3 mRNA和蛋白质丰度在雄性腺泡中显著高于雌性腺泡。KCNE 2在雄性和雌性（发情期）结肠隐窝中无表达，KCNQ 1在雄性和雌性（发情期）结肠隐窝中的表达无差异。男性隐窝显示出2.2倍的高水平的协会KCNQ 1和KCNE 3相比，女性细胞。在雌性结肠隐窝中，KCNQ 1和KCNE 3蛋白表达在整个发情周期中波动，17 β-雌二醇（E2 10 nM）产生快速（
The KCNQ1 potassium channel associates with various KCNE ancillary subunits that drastically affect channel gating and pharmacology. Co-assembly with KCNE3 produces a current with nearly instantaneous activation, some time-dependent activation at very positive potentials, a linear current-voltage relationship and a 10-fold higher sensitivity to chromanol 293B. KCNQ1: KCNE3 channels are expressed in colonic crypts and mediate basolateral K+ recycling required for Cl- secretion. We have previously reported the female-specific anti-secretory effects of oestrogen via KCNQ1: KCNE3 channel inhibition in colonic crypts. This study was designed to determine whether sex and oestrogen regulate the expression and function of KCNQ1 and KCNE3 in rat distal colon. Colonic crypts were isolated from Sprague-Dawley rats and used for whole-cell patch-clamp and to extract total RNA and protein. Sheets of epithelium were used for short-circuit current recordings. KCNE1 and KCNE3 mRNA and protein abundance were significantly higher in male than female crypts. No expression of KCNE2 was found and no difference was observed in KCNQ1 expression between male and female (at oestrus) colonic crypts. Male crypts showed a 2.2-fold higher level of association of KCNQ1 and KCNE3 compared to female cells. In female colonic crypts, KCNQ1 and KCNE3 protein expression fluctuated throughout the oestrous cycle and 17 beta-oestradiol (E2 10 nM) produced a rapid (