Role of the amino-terminal transmembrane domain of sulfonylurea receptor SUR2B for coupling to K(IR)6.2, ligand binding, and oligomerization.

ATP-sensitive K(+) (K(ATP)) channels consist of two types of subunits, K(IR)6.x that form the pore, and sulfonylurea receptors (SURs) that serve as regulatory subunits. SURs are ATP-binding cassette (ABC) proteins and contain, in addition to two nucleotide binding folds, the binding sites for channel openers such as diazoxide and P1075 and channel inhibitors such as glibenclamide (GBC) and repaglinide.

Importance of the Kir6.2 N-terminus for the interaction of glibenclamide and repaglinide with the pancreatic K(ATP) channel.

The pancreatic K(ATP) channel, SUR1/Kir6.2, couples insulin secretion to the plasma glucose level. The channel is an octamer with four Kir6.

Substitution of the Walker A lysine by arginine in the nucleotide-binding domains of sulphonylurea receptor SUR2B: effects on ligand binding and channel activity.

Sulphonylurea receptors (SURs) serve as regulatory subunits of ATP-sensitive K(+) channels. SURs are members of the ATP-binding cassette (ABC) protein superfamily and contain two conserved nucleotide-binding domains (NBDs) which bind and hydrolyse MgATP; in addition, they carry the binding sites for the sulphonylureas like glibenclamide (GBC) which close the channel and for the K(ATP) channel openers such as P1075. Here we have exchanged the conserved Lys in the Walker A motif by Arg in both NBDs of SUR2B, the regulatory subunit of the vascular K(ATP) channel.

Cyclic AMP increases cytoplasmic free calcium in renin-secreting cells from rat kidney.

The renin-secreting juxtaglomerular cells (JGC) in the media of the afferent arteriole at the vessel pole are the major source of circulating renin. The control of renin secretion is complex with increases in cAMP being the major stimulus and increases in intracellular free Ca2+ concentration ([Ca2+]i) being inhibitory. We measured [Ca2+]i in the afferent arteriole from mostly JGC.

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

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).