PT  - JOURNAL ARTICLE
AU  - Duprat, Fabrice
AU  - Lesage, Florian
AU  - Patel, Amanda J.
AU  - Fink, Michel
AU  - Romey, Georges
AU  - Lazdunski, Michel
TI  - The Neuroprotective Agent Riluzole Activates the Two  P Domain K<sup>+</sup> Channels TREK-1 and TRAAK
DP  - 2000 May 01
TA  - Molecular Pharmacology
PG  - 906--912
VI  - 57
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/57/5/906.short
4100  - http://molpharm.aspetjournals.org/content/57/5/906.full
SO  - Mol Pharmacol2000 May 01; 57
AB  - Riluzole (RP 54274) is a potent neuroprotective agent with anticonvulsant, sedative, and anti-ischemic properties. It is currently used in the treatment of amyotrophic lateral sclerosis. This article reports that riluzole is an activator of TREK-1 and TRAAK, two important members of a new structural family of mammalian background K+ channels with four transmembrane domains and two pore regions. Whereas riluzole activation of TRAAK is sustained, activation of TREK-1 is transient and is followed by an inhibition. The inhibitory process is attributable to an increase of the intracellular cAMP concentration by riluzole that produces a protein kinase A-dependent inhibition of TREK-1. Mutants of TREK-1 lacking the Ser residue where the kinase A phosphorylation takes place are activated in a sustained manner by riluzole. TRAAK is permanently activated by riluzole because, unlike TREK-1, it lacks the negative regulation by cAMP. The American Society for Pharmacology and Experimental Therapeutics