Cloning and functional expression of the cDNA encoding an inwardly-rectifying potassium channel expressed in pancreatic β-cells and in the brain

• Published in: FEBS letters Vol. 367; no. 1; pp. 61 - 66
• Main Authors: Bond, C.T., Ämmälä, C., Ashfield, R., Blair, T.A., Gribble, F., Khan, R.N., Lee, K., Proks, P., Rowe, I.C.M., Sakura, H., Ashford, M.J., Adelman, J.P., Ashcroft, F.M.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 19.06.1995
• Subjects: Amino Acid Sequence; Animals; ATP-sensitive K-channel; Base Sequence; BIR1; Brain - metabolism; Cloning, Molecular; DNA, Complementary - genetics; DNA, Complementary - isolation & purification; Humans; Insulinoma - metabolism; Inward rectifyer; Islets of Langerhans - metabolism; K-channel; Molecular Sequence Data; Pancreatic β-cell; Patch-Clamp Techniques; Potassium Channels - biosynthesis; Potassium Channels - genetics; Rats; Sequence Alignment; Tumor Cells, Cultured; Xenopus; BIR1; Pancreatic β-cell; K-channel; Inward rectifyer; ATP-sensitive K-channel
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(95)00497-W

A cDNA clone encoding an inwardly-rectifying K-channel (BIR1) was isolated from insulinoma cells. The predicted amino acid sequence shares 72% identity with the cardiac ATP-sensitive K-channel rcK ATP (K ATP-1; [6]). The mRNA is expressed in the brain and insulinoma cells. Heterologous expression in Xenopus oocytes produced currents which were K +-selective, time-independent and showed inward rectification. The currents were blocked by external barium and caesium, but insensitive to tolbutamide and diazoxide. In inside-out patches, channel activity was not blocked by 1 mM internal ATP. The sequence homology with K ATP-1 suggests that BIR1 is a subunit of a brain and β-cell K ATP channel. However, pharmacological differences and the lack of ATP-sensitivity, suggest that if, this is the case, heterologous subunits must exert strong modulatory influences on the native channel.