Volatile anesthetics activate the human tandem pore domain baseline K+ channel KCNK5.
BACKGROUND
Previous studies have identified a volatile anesthetic-induced increase in baseline potassium permeability and concomitant neuronal inhibition. The emerging family of tandem pore domain potassium channels seems to function as baseline potassium channels in vivo. Therefore, we studied the effects of clinically used volatile anesthetics on a recently described member of this family.


METHODS
A cDNA clone containing the coding sequence of KCNK5 was isolated from a human brain library. Expression of KCNK5 in the central nervous system was determined by Northern blot analysis and reverse-transcription polymerase chain reaction. Functional expression of the channel was achieved by injection of cRNA into Xenopus laevis oocytes.


RESULTS
Expression of KCNK5 was detected in cerebral cortex, medulla, and spinal cord. When heterologously expressed in Xenopus oocytes, KCNK5 currents exhibited delayed activation, outward rectification, proton sensitivity, and modulation by protein kinase C. Clinical concentrations of volatile general anesthetics potentiated KCNK5 currents by 8-30%.


CONCLUSIONS
Human KCNK5 is a tandem pore domain potassium channel exhibiting delayed activation and sensitivity to volatile anesthetics and may therefore have a role in suppressing cellular excitability during general anesthesia.
Gray
A T
AT
Department of Anesthesia and Perioperative Care, University of California, San Francisco, California, USA.
Zhao
B B
BB
Kindler
C H
CH
Winegar
B D
BD
Mazurek
M J
MJ
Xu
J
J
Chavez
R A
RA
Forsayeth
J R
JR
Yost
C S
CS
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D003001:Cloning, Molecular; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D017933:Peripheral Nervous System; D015221:Potassium Channels / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism; D014018:Tissue Distribution; D014982:Xenopus laevis
D018685:Anesthetics, Inhalation; C410295:KCNK5 protein, human; C498740:Kcnk5 protein, rat; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain