Barfod E T, Moore A L, Lidofsky S D
Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
Am J Physiol Cell Physiol. 2001 Apr;280(4):C836-42. doi: 10.1152/ajpcell.2001.280.4.C836.
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 (EC(50) 630 nM) and were blocked by the SK channel inhibitor apamin (IC(50) 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.
小电导钙激活钾（SK）通道已从哺乳动物大脑中克隆出来，但对于非兴奋性组织中SK通道的分子特征知之甚少。在此，我们报告从大鼠肝脏中分离出SK3的一种同工型。大鼠肝脏同工型的序列在NH3末端的五个氨基酸残基上与大鼠脑SK3不同，在这方面它更类似于人类脑SK3。在大鼠肝脏的肝细胞和HTC大鼠肝癌细胞中可检测到SK3免疫反应性。用肝脏SK3转染的人胚肾（HEK - 293）细胞表达10 pS的钾通道，这些通道依赖于Ca2 +（EC50为630 nM），并被SK通道抑制剂蜂毒明肽阻断（IC50为0.6 nM）；全细胞SK3电流在膜电位高于 - 40 mV时失活。值得注意的是，SK3的Ca2 +依赖性、蜂毒明肽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一种可能性，即SK3通道在肝损伤期间影响肝胆细胞的膜钾通透性。
