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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
MODULATION OF SODIUM CURRENTS IN MICE DORSAL ROOT GANGLION (DRG) NEURONS BY INTERLEUKIN-17A (IL-17A)
Abstract number: P105
Natura
1
*G.
, Hoffmann
2
B., Heinemann
3
S.H., Schaible
1
H.-G.
1
Friedrich Schiller University Jena, University Hospital, Insitute of Physiology I, Jena, Germany
2
Friedrich Schiller University, Biomolecular Photonics Group, Jena, Germany
3
Friedrich Schiller University, Center for Molecular Biomedicine, Dept. Biophysics, Jena, Germany
Interleukin-17A (IL-17A) is a proinflammatory cytokine which is important in autoimmune diseases such as rheumatoid arthritis. Recently we found that IL-17A is also pronociceptive. A large proportion of dorsal root ganglion (DRG) cells express IL-17A receptors, and application of IL-17A into the rat knee joint sensitized nociceptive joint afferents to mechanical stimuli. Interestingly, however, a low concentration of IL-17A reduced the responses of Aδ fibers to mechanical stimulation. In order to further explore the role of IL-17A in nociception we studied here the effect of IL-17A on Na+ currents in small- to medium-sized mouse DRG neurons using patch-clamp recordings. We used either WT mice, Nav1.8 or Nav1.9 knockout mice. IL-17A was applied to the bath at doses of 10 and 100 ng/ml, and we tested its effect on the magnitude of different types of Na+ currents. In part of the experiments we administered TTX 500 nM to the bath. After bath application of 100 ng/ml IL-17A, WT mice exhibited an increase of TTX resistant Na+ currents of about 25%. In Nav1.9-/- mice TTX resistant Na+ currents increased by about 30%. In Nav1.8-/- mice, without TTX, we found a reduction of Na+ currents by 70%. After bath application of 10 ng/ml IL-17A, the increase of Na+ currents was between 5% and 10%, whereas the reduction of TTX sensitive currents was about 50%. From these experiments we conclude that IL-17A increases TTX resistant Na+ currents but rather decreases TTX sensitive Na+ currents. These findings may explain the response pattern described above.
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Acta Physiologica 2013; Volume 207, Supplement 694 :P105