ATP-sensitive potassium channels: Diverse functions in the central nervous system

ATP-sensitive potassium channels open when cytoplasmic levels of ATP drop, thus linking membrane potential to the metabolic state of the cell. Cloning studies have suggested that these channels are related structurally to the inward rectifier family of potassium channels, with two putative membrane-spanning regions. Sulfonylurea drugs, which are used in the treatment of diabetes, inhibit these channels by binding to an associated membrane protein, Other drugs, including some vasodilators, activate ATP-sensitive potassium channels. Diverse neurotransmitter and hormone receptors can modulate these channels, in some cases through interactions with guanyl nucleotide binding proteins. There appear to be multiple subtypes of these channels, differing in electrical properties as well as in drug sensitivities. In the brain, these channels appear to play a role in mediating satiety after feeding. They also function in neurons to protect against excitotoxicity, by counteracting the membrane depolarization associated with metabolic stress. Brain dopamine receptors appear to modulate a novel subtype of ATP-sensitive potassium channel. The association of dopamine receptors with a mechanism involved in protection against neurodegeneration may have implications for the causes of diseases in which dopaminergic regions of brain undergo structural changes, possibly including schizophrenia.