Harinath, S and Sikdar, SK (2004) Trichloroethanol enhances the activity ofrecombinant human TREK-1 and TRAAK channels. In: Neuropharmacology, 46 (5). pp. 750-760.
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Human TREK-1 and TRAAK (hTREK-1 and hTRAAK) are the recently cloned tandem pore-domain potassium channels that are highly expressed in the central nervous system (CNS). The roles of2P domain $K^+$ channels in general anesthesia and neuroprotection have been proposed recently. We have investigated the ability of2,2,2-trichloroethanol (an active metabolite of the general anesthetic chloral hydrate (CH)) to modulate the activity ofhTREK-1 and hTRAAK channels expressed heterologously in Chinese hamster ovary cells by using whole-cell patch-clamp recording. Trichloroethanol potentiated hTREK-1 and hTRAAK channel activity in a reversible, concentration-dependent manner. The parent compound CH also augmented the activity ofboth the channels reversibly. CH activation of hTREK-1 was transient followed by a rapid inhibition, whereas hTRAAK activation was not followed by inhibition. Deletions of the carboxy terminal domain (D89, D100 and D119) of hTREK-1 did not abolish sensitivity to TCE (20 mM) suggesting that C-terminal tail is not essential for the activation of hTREK-1 by TCE. The hTREK-1 currents consisted of an instantaneous and a time-dependent component. The time-dependent current was reduced by trichloroethanol (20 mM). Our findings identify TREK-1 and TRAAK channels as molecular targets for trichloroethanol and suggest that activation ofthese channels might contribute to the CNS depressant effects ofCH.
|Item Type:||Journal Article|
|Additional Information:||The copyright belongs to Elsevier.|
|Keywords:||Anesthetic;Chloral hydrate;TREK-1 channel;TRAAK channel;Trichloroethanol;Whole-cell patch-clamp recording|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit|
|Date Deposited:||27 May 2006|
|Last Modified:||19 Sep 2010 04:27|
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