Pancreatic Islet Cells Express a Family of Inwardly Rectifying K+ Channel Subunits Which Interact to Form G-protein-activated Channels (∗)

Insulin secretion is associated with changes in pancreatic β-cell K+ permeability. A degenerate polymerase chain reaction strategy based on the conserved features of known inwardly rectifying K+ (KIR) channel genes was used to identify members of this family expressed in human pancreatic islets and...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-11, Vol.270 (44), p.26086-26091
Main Authors: Ferrer, Jorge, Nichols, Colin G., Makhina, Elena N., Salkoff, Lawrence, Bernstein, Josh, Gerhard, Daniella, Wasson, Jonathan, Ramanadham, Sasanka, Permutt, Alan
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Cloning, Molecular
DNA Primers
Female
Gene Expression
Gene Library
GTP-Binding Proteins - metabolism
Humans
Insulinoma - metabolism
Islets of Langerhans - metabolism
Kinetics
Macromolecular Substances
Membrane Potentials
Mice
Molecular Sequence Data
Oocytes - physiology
Organ Specificity
Pancreatic Neoplasms - metabolism
Polymerase Chain Reaction
Potassium Channels - biosynthesis
Potassium Channels - metabolism
Potassium Channels - physiology
Potassium Channels, Inwardly Rectifying
Rats
Rats, Wistar
Recombinant Proteins - biosynthesis
Recombinant Proteins - metabolism
Sequence Homology, Amino Acid
Xenopus
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Summary:Insulin secretion is associated with changes in pancreatic β-cell K+ permeability. A degenerate polymerase chain reaction strategy based on the conserved features of known inwardly rectifying K+ (KIR) channel genes was used to identify members of this family expressed in human pancreatic islets and insulinoma. Three related human KIR transcript sequences were found: CIR (also known as cardiac KATP-1), GIRK1, and GIRK2 (KATP-2). The pancreatic islet CIR and GIRK2 full-length cDNAs were cloned, and their genes were localized to human chromosomes 11q23-ter and 21, respectively. Northern blot analysis detected CIR mRNA at similar levels in human islets and exocrine pancreas, while the abundance of GIRK2 mRNA in the two tissues was insufficient for detection by this method. Using competitive reverse-transcription polymerase chain reaction, CIR was found to be present at higher levels than GIRK2 mRNA in native purified β-cells. Xenopus oocytes injected with M2 muscarinic receptor (M2) plus either GIRK2 or CIR cRNA expressed only very small carbachol-induced currents, while co-injection of CIR plus GIRK2 along with M2 resulted in expression of carbachol-activated strong inwardly rectifying currents. Activators of KATP channels failed to elicit currents in the presence or absence of co-expressed sulfonylurea receptor. These results show that two components of islet cell KIR channels, CIR and GIRK2, may interact to form heteromeric G-protein-activated inwardly rectifying K+ channels that do not possess the typical properties of KATP channels.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.270.44.26086