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Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain.

Mathie, Alistair, Veale, Emma L. (2014) Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain. Pflügers Archiv : European journal of physiology, 467 (5). pp. 931-43. ISSN 0031-6768. E-ISSN 1432-2013. (doi:10.1007/s00424-014-1655-3) (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)

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. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1007/s00424-014-1655-3

Abstract

Recent evidence points to a pivotal contribution of a variety of different potassium channels, including two-pore domain potassium (K2P) channels, in chronic pain processing. Expression of several different K2P channel subunits has been detected in nociceptive dorsal root ganglion neurons and trigeminal ganglion neurons, in particular, TREK1, TREK2, TRESK, TRAAK, TASK3 and TWIK1 channels. Of these, the strongest body of evidence from functional studies highlights the importance of TREK1, TRESK and, recently, TREK2 channels. For example, TREK1 knockout mice are more sensitive than wild-type mice to a number of painful stimuli but less sensitive to morphine-induced analgesia. TRESK knockdown mice show behavioural evidence of increased pain and increased sensitivity to painful pressure. Importantly, familial migraine with aura is associated with a dominant-negative mutation in human TRESK channels. Thus, the functional up-regulation of K2P channel activity may be a useful strategy in the development of new therapies for the treatment of pain. Whilst there are few currently available compounds that selectively and directly enhance the activity of TRESK and TREK2 channels, recent advances have been made in terms of identifying compounds that activate TREK1 channels and in understanding how they might act on the channel. Large-scale bio-informatic approaches and the further development of databases of putative ligands, channel structures and putative ligand binding sites on these structures may form the basis for future experimental strategies to detect novel molecules acting to enhance K2P channel activity that would be useful in the treatment of pain.

Item Type: Article
DOI/Identification number: 10.1007/s00424-014-1655-3
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Emma Veale
Date Deposited: 04 Dec 2015 13:30 UTC
Last Modified: 29 May 2019 16:36 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/52692 (The current URI for this page, for reference purposes)
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