Cloning and functional expression of a liver isoform of the small conductance Ca 2+ -activated K + channel SK3

• Published in: American Journal of Physiology: Cell Physiology 2001-04, Vol.280 (4), p.C836-C842
• Main Authors: Barfod, Elisabeth T., Moore, Ann L., Lidofsky, Steven D.
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.2001.280.4.C836

Small conductance Ca 2+ -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 NH 3 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 Ca 2+ 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 Ca 2+ 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.