CLONING AND FUNCTIONAL EXPRESSION OF THE CDNA-ENCODING AN INWARDLY-RECTIFYING POTASSIUM CHANNEL EXPRESSED IN PANCREATIC BETA-CELLS AND IN THE BRAIN

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 beta-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.