Sulfonylurea receptors set the maximal open probability, ATP sensitivity and plasma membrane density of KATP channels

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Sulfonylurea and K+-Channel Opener Sensitivity of KATP Channels

The sensitivity of K(ATP) channels to high-affinity block by sulfonylureas and to stimulation by K(+) channel openers and MgADP (PCOs) is conferred by the regulatory sulfonylurea receptor (SUR) subunit, whereas ATP inhibits the channel through interaction with the inward rectifier (Kir6.2) subunit. Phosphatidylinositol 4, 5-bisphosphate (PIP(2)) profoundly antagonized ATP inhibition of K(ATP) c...

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Understanding mechanisms by which glibenclamide stimulates insulin release is important, particularly given recent promising treatment by glibenclamide of permanent neonatal diabetic subjects. Antidiabetic sulfonylureas are thought to stimulate insulin secretion solely by inhibiting their high-affinity ATP-sensitive potassium (K(ATP)) channel receptors at the plasma membrane of beta-cells. This...

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Anti-Diabetic Sulfonylurea Stimulates Insulin Secretion Independent of Plasma Membrane KATP Channels

Understanding mechanisms by which glibenclamide stimulates insulin release is important particularly given recent promising treatment by glibenclamide of permanent neonatal diabetic subjects. Anti-diabetic sulfonylureas are thought to stimulate insulin secretion solely by inhibiting their high affinity KATP channel receptors at the plasma membrane of β cells. This normally occurs during glucose...

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How ATP Inhibits the Open KATP Channel

ATP-sensitive potassium (K(ATP)) channels are composed of four pore-forming Kir6.2 subunits and four regulatory SUR1 subunits. Binding of ATP to Kir6.2 leads to inhibition of channel activity. Because there are four subunits and thus four ATP-binding sites, four binding events are possible. ATP binds to both the open and closed states of the channel and produces a decrease in the mean open time...

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A Family of Sulfonylurea Receptors Determines the Pharmacological Properties of ATP-Sensitive K+ Channels

We have cloned an isoform of the sulfonylurea receptor (SUR), designated SUR2. Coexpression of SUR2 and the inward rectifier K+ channel subunit Kir6.2 in COS1 cells reconstitutes the properties of K(ATP) channels described in cardiac and skeletal muscle. The SUR2/Kir6.2 channel is less sensitive than the SUR/Kir6.2 channel (the pancreatic beta cell KATP channel) to both ATP and the sulfonylurea...

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ژورنال

عنوان ژورنال: FEBS Letters

سال: 1999

ISSN: 0014-5793

DOI: 10.1016/s0014-5793(99)00102-7