title: Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP.
abstract: Neuronal stressors such as hypoxia and firing of action potentials at very high frequencies cause intracellular Na+ to rise and ATP to be consumed faster than it can be regenerated. We report the cloning of a gene encoding a K+ channel, Slick, and demonstrate that functionally it is a hybrid between two classes of K+ channels, Na+-activated (KNa) and ATP-sensitive (KATP) K+ channels. The Slick channel is activated by intracellular Na+ and Cl- and is inhibited by intracellular ATP. Slick is widely expressed in the CNS and is detected in heart. We identify a consensus ATP binding site near the C terminus of the channel that is required for ATP and its nonhydrolyzable analogs to reduce open probability. The convergence of Na+, Cl-, and ATP sensitivity in one channel may endow Slick with the ability to integrate multiple indicators of the metabolic state of a cell and to adjust electrical activity appropriately.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Arin
authors.initials: A
authors.lastname: Bhattacharjee
authors.forename: William J
authors.initials: WJ
authors.lastname: Joiner
authors.forename: Meilin
authors.initials: M
authors.lastname: Wu
authors.forename: Youshan
authors.initials: Y
authors.lastname: Yang
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Sigworth
authors.forename: Leonard K
authors.initials: LK
authors.lastname: Kaczmarek
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D003001:Cloning, Molecular; D006224:Cricetinae; D004553:Electric Conductivity; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D000081033:Potassium Channels, Sodium-Activated; D051381:Rats; D016415:Sequence Alignment; D012964:Sodium / Q000494:pharmacology*; D014018:Tissue Distribution; D014981:Xenopus
chemical_list: D002712:Chlorides; C480494:KCNT2 protein, human; C480493:Kcnt2 potassium channel, rat; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated; D000255:Adenosine Triphosphate; D012964:Sodium