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XB-ART-50997
Sci Rep September 21, 2015; 5 12548.
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Activation of TRESK channels by the inflammatory mediator lysophosphatidic acid balances nociceptive signalling.

Kollert S , Dombert B , Döring F , Wischmeyer E .


Abstract
In dorsal root ganglia (DRG) neurons TRESK channels constitute a major current component of the standing outward current IKSO. A prominent physiological role of TRESK has been attributed to pain sensation. During inflammation mediators of pain e.g. lysophosphatidic acid (LPA) are released and modulate nociception. We demonstrate co-expression of TRESK and LPA receptors in DRG neurons. Heterologous expression of TRESK and LPA receptors in Xenopus oocytes revealed augmentation of basal K(+) currents upon LPA application. In DRG neurons nociception can result from TRPV1 activation by capsaicin or LPA. Upon co-expression in Xenopus oocytes LPA simultaneously increased both depolarising TRPV1 and hyperpolarising TRESK currents. Patch-clamp recordings in cultured DRG neurons from TRESK[wt] mice displayed increased IKSO after application of LPA whereas under these conditions IKSO in neurons from TRESK[ko] mice remained unaltered. Under current-clamp conditions LPA application differentially modulated excitability in these genotypes upon depolarising pulses. Spike frequency was attenuated in TRESK[wt] neurons and, in contrast, augmented in TRESK[ko] neurons. Accordingly, excitation of nociceptive neurons by LPA is balanced by co-activation of TRESK channels. Hence excitation of sensory neurons is strongly controlled by the activity of TRESK channels, which therefore are good candidates for the treatment of pain disorders.

PubMed ID: 26224542
PMC ID: PMC4519772
Article link: Sci Rep


Species referenced: Xenopus
Genes referenced: bdkrb2 drg1 dtl htr2c kcnk18 lpar2 myc ppp3ca trpv1


Article Images: [+] show captions
References [+] :
Alloui, TREK-1, a K+ channel involved in polymodal pain perception. 2006, Pubmed