Hanyang Med Rev.  2008 Nov;28(4):63-72.

Volatile General Anesthetics and Tandem Pore Domain K+ Channel

• Shin WJ

Abstract

Two-pore domain K+ (K2P) channels are recently described. They have properties of background K+ channels, and play a crucial role in setting the resting membrane potential and regulating cell excitability. Mammalian family of K2P channel proteins are encoded by 17 KCNK genes and subdivided into 6 subfamilies on the basis of sequence similarities: TWIK, TREK, TASK, TALK, THIK, and TRESK (TWIK related spinal cord K+ channel). TWIK is weakly inward-rectifying, and TASK (acid sensitive) is a background outward-rectifiers whose activity is inhibited by low pH. TREK and TRAAK (TWIK related arachidonic acid-stimulated K+ channel) are both outward-rectifiers that are activated by polyunsaturated fatty acids, including arachidonic acid. The alkaline-activated K2P channel TALK-1 is primarily expressed in the pancreas. THIK is halothane-inhibited K+ channel. TRESK is a TWIK related spinal cord K+ channel. Many studies with volatile general anesthetics were performed using the patch-clamp technique and they showed the activation of K+ currents and they suggested that the K2P channels might be an another plausible group of targets for general anesthetics. An appreciation of how general anesthetics modulate the activity of K2P channels at the molecular level will be enhanced by future studies using site-directed mutagenesis, high-resolution structural approaches, and molecular dynamics simulations.

Keyword

KCNK; patch-clamp technique; tandem pore domain K+ channels; volatile general anesthetics

MeSH Terms

Anesthetics, General
Arachidonic Acid
Fatty Acids, Unsaturated
Humans
Hydrogen-Ion Concentration
Membrane Potentials
Mutagenesis, Site-Directed
Pancreas
Patch-Clamp Techniques
Proteins
Spinal Cord
Anesthetics, General
Arachidonic Acid
Fatty Acids, Unsaturated
Proteins