Large-conductance Ca
2+-activated K
+ (BK) channel regulates action potential firing in pancreatic
β-cells. We cloned novel spliced variants of the BK-channel
β2-subunit (BK
β2b), which consisted of 36 amino acids including the N-terminal in the original human BK
β2 (BK
β2a), from human and rodent pancreas. Real-time PCR analysis showed the abundant expression of BK
β2b transcripts in human and rodent pancreas and also in the RINm5f insulinoma cell line. In addition, up-regulation of both BK-channel
α-subunit (BK
α) and BK
β2b transcripts was observed in pancreas tissues from diabetes mellitus patients. In HEK293 cells co-expressing BK
α and BK
β2b, the inactivation of BK-channel currents, which is typical for BK
α + BK
β2a, was not observed, and electrophysiological and pharmacological properties of BK
α + BK
β2b were almost identical to those of BK
α alone. In HEK293 cells stably expressing BK
α, the transient co-expression of yellow fluorescence protein (YFP)-tagged BK
β2a proteins resulted in their distribution along the cell membrane. In contrast, the co-expression of YFP-tagged BK
β2b with BK
α showed diffusely distributed fluorescence signals throughout the cell body. Taken together, the predominant splicing of BK
β2b versus that of BK
β2a presumably enhances the contribution of BK channels to membrane potential and may possibly be a factor modulating insulin secretion in a suppressive manner in pancreatic
β-cells.
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