Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels

Harinath, S. ; Sikdar, S. K. (2004) Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels Neuropharmacology, 46 (5). pp. 750-760. ISSN 0028-3908

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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 of 2P domain K+ channels in general anesthesia and neuroprotection have been proposed recently. We have investigated the ability of 2,2,2-trichloroethanol (an active metabolite of the general anesthetic chloral hydrate (CH)) to modulate the activity of hTREK-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 of both 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 (Δ89, Δ100 and Δ119) 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 of these channels might contribute to the CNS depressant effects of CH.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Anesthetic; Chloral Hydrate; Trek-1 Channel; Traak Channel; Trichloroethanol; Whole-cell Patch-clamp Recording
ID Code:84770
Deposited On:27 Feb 2012 13:39
Last Modified:27 Feb 2012 13:39

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