A composition comprising a novel Ca2+-activated, [ATP]i-sensitive nonspecificcation (NCCa-ATP) channel is described. The channel is found in mammalianneural cells and exhibits a different sensitivity to block by various adeninenucleotides, and is activated by submicromolar [Ca]i. The NCCa-ATP channel isactivated under conditions of ATP depletion, which causes severe celldepolarization, followed by cell swelling. The NCCa-ATP channel is regulatedby a sulfonylurea receptor and is inhibited by sulfonylurea compoundsglibenclamide and tolbutamide. Methods employing compositions comprising theNCCa-ATP channel to screen for compounds that block the channel and the use ofsuch antagonists as therapeutics in preventing brain swelling and damage aredescribed. In addition, methods employing compositions comprising the Kir2.3channel to screen for compounds that open the channel and the use of suchantagonists as therapeutics in preventing brain swelling and damage aredescribed.
