KATPkanalen

KATPkanalen (ATP-sensitive potassium channels) are a family of inward-rectifier potassium channels that link the cellular metabolic state to membrane excitability. They are widely expressed in pancreatic beta cells, cardiac and smooth muscle, neurons and other tissues, where they help tune electrical activity to energy availability.

Structure and subunits: Each channel is a hetero-octamer consisting of four Kir6.x pore-forming subunits (Kir6.1 or Kir6.2) and four regulatory sulfonylurea receptor (SUR) subunits (SUR1, SUR2A, or SUR2B). The specific Kir6/SUR combination determines tissue distribution and pharmacological properties. The channel pores allow K+ flux when open, contributing to the resting membrane potential.

Gating and regulation: The channel is inhibited by intracellular ATP binding to Kir6.x, which closes the channel when cellular energy is high. It is activated by Mg-ADP binding to SUR subunits, which promotes opening of the channel as the cell’s energy state declines. This coupling links metabolism to electrical excitability.

Physiological roles: In pancreatic beta cells, KATP channels couple glucose metabolism to insulin secretion: rising ATP after glucose metabolism closes the channels, leading to depolarization, opening of voltage-gated Ca2+ channels, and insulin release. In cardiac and smooth muscle, they help regulate vascular tone and protect cells during metabolic stress by limiting excitability. In neurons, they modulate excitability and neurotransmission. During ischemia or metabolic stress, opening of KATP channels can shorten action potentials and reduce energy demand.

Pharmacology and clinical significance: Sulfonylureas (for example, glibenclamide) block KATP channels to promote insulin secretion in type 2 diabetes. Diazoxide and related drugs open KATP channels, used to treat hyperinsulinemia and certain hypertensive emergencies. Mutations in KCNJ11 (Kir6.2) or ABCC8 (SUR1) can cause neonatal diabetes or congenital hyperinsulinism, underscoring the channel’s role in metabolic control. Mitochondrial KATP channels (mitoKATP) are proposed regulators of mitochondrial function, though their molecular identity remains debated.