Cloning and functional expression of a liver isoform of the small conductance Ca2+-activated K+ channel SK3.
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.
Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
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ET
Barfod
A L
AL
Moore
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SD
Lidofsky
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D022781:Hepatocytes / Q000737:chemistry; D006801:Humans; D007536:Isomerism; D007668:Kidney / Q000166:cytology; D008099:Liver / Q000737:chemistry* / Q000378:metabolism*; D008113:Liver Neoplasms; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D017386:Sequence Homology, Amino Acid; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014162:Transfection; D014407:Tumor Cells, Cultured
C496901:Kcnn3 protein, rat; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D011188:Potassium; D002118:Calcium