TY  - JOUR
A1  - Kollert, Sina
A1  - Dombert, Benjamin
A1  - Döring, Frank
A1  - Wischmeyer, Erhard
T1  - Activation of TRESK channels by the inflammatory mediator lysophosphatidic acid balances nociceptive signalling
JF  - Scientific Reports
N2  - In dorsal root ganglia (DRG) neurons TRESK channels constitute a major current component of the standing outward current IK\(_{SO}\). 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 TRPV\(_{1}\) activation by capsaicin or LPA. Upon co-expression in Xenopus oocytes LPA simultaneously increased both depolarising TRPV\(_{1}\) and hyperpolarising TRESK currents. Patch-clamp recordings in cultured DRG neurons from TRESK[wt] mice displayed increased IK\(_{SO}\) after application of LPA whereas under these conditions IK\(_{SO}\) 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.
KW  - protein coupled receptors
KW  - molecular mechanisms
KW  - neuropathic pain
KW  - migraine
KW  - initiation
KW  - modulation
KW  - cells
KW  - sensory neurons
KW  - domain K\(^{+}\) channels
KW  - 2-pore potassium channel
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148312
VL  - 5
IS  - 12548
ER  - 
TY  - JOUR
A1  - Forconi, Mariko
A1  - Canapa, Adriana
A1  - Barucca, Marco
A1  - Biscotti, Maria A.
A1  - Capriglione, Teresa
A1  - Buonocore, Francesco
A1  - Fausto, Anna M.
A1  - Makapedua, Daisy M.
A1  - Pallavicini, Alberto
A1  - Gerdol, Marco
A1  - De Moro, Gianluca
A1  - Scapigliati, Giuseppe
A1  - Olmo, Ettore
A1  - Schartl, Manfred
T1  - Characterization of Sex Determination and Sex Differentiation Genes in Latimeria
JF  - PLoS ONE
N2  - Genes involved in sex determination and differentiation have been identified in mice, humans, chickens, reptiles, amphibians and teleost fishes. However, little is known of their functional conservation, and it is unclear whether there is a common set of genes shared by all vertebrates. Coelacanths, basal Sarcopterygians and unique "living fossils", could help establish an inventory of the ancestral genes involved in these important developmental processes and provide insights into their components. In this study 33 genes from the genome of Latimeria chalumnae and from the liver and testis transcriptomes of Latimeria menadoensis, implicated in sex determination and differentiation, were identified and characterized and their expression levels measured. Interesting findings were obtained for GSDF, previously identified only in teleosts and now characterized for the first time in the sarcopterygian lineage; FGF9, which is not found in teleosts; and DMRT1, whose expression in adult gonads has recently been related to maintenance of sexual identity. The gene repertoire and testis-specific gene expression documented in coelacanths demonstrate a greater similarity to modern fishes and point to unexpected changes in the gene regulatory network governing sexual development.
KW  - medaka fish
KW  - mullerian hormone AMH
KW  - DM-domain gene
KW  - oryzias latipes
KW  - monodelphis domestica
KW  - oreochromis niloticus
KW  - dimorphic expression
KW  - molecular mechanisms
KW  - genomic organization
KW  - regulatory regions
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130995
VL  - 8
IS  - 4
ER  -