Gruss, Marco and Bushell, Trevor J. and Bright, D.P. and Lieb, William R. and Mathie, Alistair and Franks, Nicholas P. (2004) Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Molecular Pharmacology, 65 (2). pp. 443-452. ISSN 0026-895X . (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)
Nitrous oxide, xenon, and cyclopropane are anesthetic gases that have a distinct pharmacological profile. Whereas the molecular basis for their anesthetic actions remains unclear, they behave very differently to most other general anesthetics in that they have little or no effect on GABAA receptors, yet strongly inhibit the N-methyl-d-aspartate subtype of glutamate receptors. Here we show that certain members of the two-pore-domain K+ channel superfamily may represent an important new target for these gaseous anesthetics. TREK-1 is markedly activated by clinically relevant concentrations of nitrous oxide, xenon, and cyclopropane. In contrast, TASK-3, a member of this family that is very sensitive to volatile anesthetics, such as halothane, is insensitive to the anesthetic gases. We demonstrate that the C-terminal cytoplasmic domain is not an absolute requirement for the actions of the gases, although it clearly plays an important modulatory role. Finally, we show that Glu306, an amino acid that has previously been found to be important in the modulation of TREK-1 by arachidonic acid, membrane stretch and internal pH, is critical for the activating effects of the anesthetic gases.
|Subjects:||Q Science > QP Physiology (Living systems)|
|Divisions:||Faculties > Science Technology and Medical Studies > Medway School of Pharmacy|
|Depositing User:||Alistair Mathie|
|Date Deposited:||28 May 2009 16:33|
|Last Modified:||30 May 2014 13:15|
|Resource URI:||https://kar.kent.ac.uk/id/eprint/5645 (The current URI for this page, for reference purposes)|