Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP

J Neurosci. 2003 Dec 17;23(37):11681-91. doi: 10.1523/JNEUROSCI.23-37-11681.2003.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Cells, Cultured
  • Chlorides / pharmacology
  • Cloning, Molecular
  • Cricetinae
  • Electric Conductivity
  • Humans
  • Ion Channel Gating
  • Kinetics
  • Molecular Sequence Data
  • Potassium Channels / genetics*
  • Potassium Channels / metabolism*
  • Potassium Channels, Sodium-Activated
  • Rats
  • Sequence Alignment
  • Sodium / pharmacology*
  • Tissue Distribution
  • Xenopus

Substances

  • Chlorides
  • KCNT2 protein, human
  • Kcnt2 potassium channel, rat
  • Potassium Channels
  • Potassium Channels, Sodium-Activated
  • Adenosine Triphosphate
  • Sodium

Associated data

  • GENBANK/AY359443
  • GENBANK/AY359444