ATP-Sensitive Potassium Channel on Pancreatic Beta Cell (KATP channel)

ATP-Sensitive Potassium Channel on Pancreatic Beta Cell Overview

The ATP-sensitive potassium channel (KATP channel) in pancreatic beta cells is a crucial molecular sensor that links cellular metabolism to electrical activity, thereby regulating insulin secretion. It plays a central role in glucose homeostasis by coupling changes in intracellular ATP/ADP ratios—reflecting metabolic status—to the membrane potential and subsequent insulin release. The KATP channel is a hetero-octameric complex composed of four pore-forming Kir6.2 subunits and four regulatory sulfonylurea receptor 1 (SUR1) subunits. At low glucose concentrations, KATP channels remain open, keeping the beta cell membrane hyperpolarized and suppressing insulin secretion. When blood glucose rises, increased metabolism elevates intracellular ATP levels. ATP binds to and inhibits KATP channels, causing them to close, leading to membrane depolarization, opening voltage-dependent calcium channels, and triggering exocytosis of insulin-containing granules. Sulfonylurea drugs bind SUR1 subunits and close the channel independently of ATP levels, stimulating insulin release. Mutations can cause neonatal diabetes (gain-of-function) or congenital hyperinsulinism (loss-of-function). Polymorphisms such as E23K in Kir6.2 are associated with an increased risk for late-onset type 2 diabetes.

Mechanism of Action

Sulfonylureas bind to SUR1 subunits and close the channel independently of ATP levels, stimulating insulin release.

Biological Functions

Safety Considerations

Interacting Drugs