| 19955488 |
Parelkar NK, Silswal N, Jansen K, Vaughn J, Bryan RM Jr, Andresen J: 2,2,2-trichloroethanol activates a nonclassical potassium channel in cerebrovascular smooth muscle and dilates the middle cerebral artery. J Pharmacol Exp Ther. 2010 Mar;332(3):803-10. Epub 2009 Dec 2.
Trichloroacetaldehyde monohydrate [chloral hydrate (CH)] is a sedative/hypnotic that increases cerebral blood flow (CBF), and its active metabolite 2,2,2-trichloroethanol (TCE) is an agonist for the nonclassical two-pore domain K (+) (K (2P)) channels TREK-1 and TRAAK. We sought to determine whether TCE dilates cerebral arteries in vitro by activating nonclassical K (+) channels. TCE dilated pressurized and perfused rat middle cerebral arteries (MCAs) in a manner consistent with activation of nonclassical K (+) channels. Dilation to TCE was inhibited by elevated external K (+) but not by an inhibitory cocktail (IC) of classical K (+) channel blockers. Patch-clamp electrophysiology revealed that, in the presence of the IC, TCE increased whole-cell currents and hyperpolarized the membrane potential of isolated MCA smooth muscle cells. Heating increased TCE-sensitive currents, indicating that the activated channel was thermosensitive. Immunofluorescence in sections of the rat MCA demonstrated that, like TREK-1, TRAAK is expressed in the smooth muscle of cerebral arteries. Isoflurane did not, however, dilate the MCA, suggesting that TREK-1 was not functional. These data indicate that TCE activated a nonclassical K (+) channel with the characteristics of TRAAK in rat MCA smooth-muscle cells. Stimulation of K (+) channels such as TRAAK in cerebral arteries may therefore explain in part how CH/TCE increases CBF. |
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