Cloning and functional expression of a liver isoform of the small conductance Ca2+-activated K+ channel SK3
Cloning and functional expression of a liver isoform of the small conductance Ca2+-activated K+ channel SK3
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DOI：
10.1152/ajpcell.2001.280.4.c836
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发表时间：
2001-04-01
影响因子：
5.5
通讯作者：
Lidofsky, SD
中科院分区：
文献类型：
--
作者：
Barfod, ET;Moore, AL;Lidofsky, SD
小电导钙激活K+(SK)通道已从哺乳动物脑中克隆出来，但对其在非兴奋性组织中的分子特性知之甚少。在此，我们报道了从大鼠肝脏中分离到SK3的异构体。大鼠肝脏亚型的序列与大鼠脑SK3的序列不同，在NH3末端有五个氨基酸残基，与人脑SK3更接近。在大鼠肝细胞和HTC大鼠肝癌细胞中均可检测到SK3免疫反应。人胚胎肾(HEK-293)细胞表达10个钙依赖性钾通道(EC50为630 nM)，并可被SK通道阻滞剂apamin阻断(IC50为0.6 nM)；膜电位大于-40 mV时，全细胞SK3电流失活。值得注意的是，SK3的钙离子依赖性、阿帕明敏感性和电压依赖性失活与代谢应激诱发的肝细胞和胆管上皮SK通道的特性惊人地相似。这些观察结果提出了SK3通道在肝损伤过程中影响肝胆管细胞膜K+通透性的可能性。
Small conductance Ca2+-activated K+ (SK) channels have been cloned from mammalian brain, but little is known about the molecular characteristics of SK channels in nonexcitable tissues. Here, we report the isolation from rat liver of an isoform of SK3. The sequence of the rat liver isoform differs from rat brain SK3 in five amino acid residues in the NH3 terminus, where it more closely resembles human brain SK3. SK3 immunoreactivity was detectable in hepatocytes in rat liver and in HTC rat hepatoma cells. Human embryonic kidney (HEK-293) cells transfected with liver SK3 expressed 10 pS K+ channels that were Ca2+ dependent (EC50 630 nM) and were blocked by the SK channel inhibitor apamin (IC50 0.6 nM); whole cell SK3 currents inactivated at membrane potentials more positive than -40 mV. Notably, the Ca2+ dependence, apamin sensitivity, and voltage-dependent inactivation of SK3 are strikingly similar to the properties of hepatocellular and biliary epithelial SK channels evoked by metabolic stress. These observations raise the possibility that SK3 channels influence membrane K+ permeability in hepatobiliary cells during liver injury.