Therapeutic potential of neuronal two-pore domain potassium-channel modulators

Mathie, A.A. and Veale, E.L. (2007) Therapeutic potential of neuronal two-pore domain potassium-channel modulators. Current Opinion in Investigational Drugs, 8 (7). pp. 555-562. ISSN 1472-4472. (The full text of this publication is not available from this repository)

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Abstract

Two-pore domain potassium (K2P) channels are expressed in cells throughout the body and give rise to leak potassium currents which control the excitability of these cells. Although not inhibited by classical potassium channel-blocking drugs, such as tetraethylammonium and 4-aminopyridine, K2P channels are regulated by a diverse array of pharmacological mediators. There are six main families of K2P channels and among these certain members of the TREK family (ie, TREK-1 and TREK-2) are activated by general anesthetic agents such as halothane, xenon and nitrous oxide. In addition, all members of the TREK family are activated by neuroprotective agents, such as riluzole, polyunsaturated fatty acids and lysophospholipids, suggesting that these channels play an important role in neuroprotection. TREK channels are also inhibited by chlorpromazine, local anesthetics and the antidepressant fluoxetine. Furthermore, all members of the TASK family are inhibited by cannabinoids and local anesthetics, and TASK-3 is selectively inhibited by ruthenium red. Thus, the diversity and physiological importance of K2P channels suggest that the development of selective compounds to target these proteins has therapeutic potential for CNS disorders such as stroke, depression and epilepsy.

Item Type: Article
Additional information: Review Article
Uncontrolled keywords: antidepressant; cannabinoid; ciclosporin; fluoxetine; general anesthetic; lysophospholipid; neuroprotection; polyunsaturated fatty acid; ruthenium red; two-pore domain potassium channel
Subjects: R Medicine > RS Pharmacy and materia medica
Q Science > QP Physiology (Living systems)
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Stephen Holland
Date Deposited: 19 Dec 2007 19:26
Last Modified: 14 Jan 2010 14:05
Resource URI: http://kar.kent.ac.uk/id/eprint/2081 (The current URI for this page, for reference purposes)
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