Tandem pore domain K channels: an important site of volatile anesthetic action?
Despite over 150 years of clinical use, the mechanism and molecular elements by which volatile anesthetics produce unconsciousness are not established. Although enhanced activity of inhibitory neurotransmitter systems (GABAA) and depression of excitatory neurotransmitter systems (NMDA) probably contribute to the anesthetic state, the role of other ion channels families have also been studied. Potassium channels represent the largest group of mammalian ion channels and their activity to reduce neuronal excitability makes them viable candidates as sites of anesthetic action. Several studies from the 1970's and 80's identified volatile anesthetic enhancement of neuronal potassium currents. More recently, a new family of K channels with a unique structure (tandem pore domains) that may be responsible for baseline or background K currents have been isolated and some members of this family can be activated by volatile anesthetics. These emerging findings suggest a new molecular mechanism by which volatile anesthetics may mediate central nervous system depression.
Yost
C S
CS
Department of Anesthesia, University of California, San Francisco 94143, USA. spyost@itsa.ucsf.edu
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D007448:Invertebrates; D007530:Isoflurane / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051637:Shaker Superfamily of Potassium Channels
D018685:Anesthetics, Inhalation; D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D007530:Isoflurane; D006221:Halothane