Cloning and functional expression of a liver isoform of the small conductance Ca2+-activated K+ channel SK3

Departments of Medicine and Pharmacology, University of Vermont, Burlington Vermont 05405 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 is...

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Bibliographic Details
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
Subjects:
Animals
Apamin - pharmacology
Calcium - metabolism
Carcinoma, Hepatocellular
Cloning, Molecular
Fluorescent Antibody Technique
Hepatocytes - chemistry
Humans
Isomerism
Kidney - cytology
Liver - chemistry
Liver - metabolism
Liver Neoplasms
Membrane Potentials - drug effects
Membrane Potentials - physiology
Molecular Sequence Data
Patch-Clamp Techniques
Potassium - metabolism
Potassium Channels - chemistry
Potassium Channels - genetics
Potassium Channels - metabolism
Potassium Channels, Calcium-Activated
Rats
Sequence Homology, Amino Acid
Small-Conductance Calcium-Activated Potassium Channels
Transfection
Tumor Cells, Cultured
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Summary:Departments of Medicine and Pharmacology, University of Vermont, Burlington Vermont 05405 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. cloning; hepatocytes; immunofluorescence; ion channels; patch clamp; transfection
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.2001.280.4.C836