Incomplete dissociation of glibenclamide from wild-type and mutant pancreatic K ATP channels limits their recovery from inhibition.

ABSTRACT:

Background and purpose

The antidiabetic sulphonylurea, glibenclamide, acts by inhibiting the pancreatic ATP-sensitive K(+) (K(ATP)) channel, a tetradimeric complex of K(IR)6.2 and sulphonylurea receptor 1 (K(IR)6.2/SUR1)(4). At room temperature, recovery of channel activity following washout of glibenclamide is very slow and cannot be measured. This study investigates the relation between the recovery of channel activity from glibenclamide inhibition and the dissociation rate of [(3)H]-glibenclamide from the channel at 37 degrees C.

Experimental approach

K(IR)6.2, K(IR)6.2DeltaN5 or K(IR)6.2DeltaN10 (the latter lacking amino-terminal residues 2-5 or 2-10 respectively) were coexpressed with SUR1 in HEK cells. Dissociation of [(3)H]-glibenclamide from the channel and recovery

SUBMITTER: Russ U 

PROVIDER: S-EPMC2697833 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature