ATP-sensitive potassium (KATP) channels couple cell metabolism to electrical activity of the plasma membrane by regulating membrane K+ fluxes. A reduction in metabolism opens KATP channels, producing K+ efflux, membrane hyperpolarization, and suppression of electrical activity. Conversely, increased metabolism closes KATP channels. The consequent membrane depolarization stimulates electrical activity and may thereby trigger cellular responses such as the release of hormones and neurotransmitters, or muscle contraction. Given their critical role in regulating electrical excitability in many cells, it is evident that disruption of KATP channel function can lead to disease. To date, mutations in KATP channel genes have been shown to cause neonatal diabetes, hyperinsulinemia, and dilated cardiomyopathy in humans. The KATP channel is an octameric complex of 4 Kir6.x and 4 SURx subunits. The pore-forming Kir6.x subunit belongs to the inwardly rectifying family of potassium channels.