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The Pentapeptide QYNAD Does Not Inhibit Neuronal Network Activity

Published online by Cambridge University Press:  02 December 2014

F. Otto ,
B.C. Kieseier ,
P. Görtz ,
H.-P. Hartung  and
M. Siebler
F. Otto
Affiliation:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Germany
B.C. Kieseier
Affiliation:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Germany
P. Görtz
Affiliation:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Germany
H.-P. Hartung
Affiliation:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Germany
M. Siebler*
Affiliation:
Department of Neurology, Heinrich-Heine-University Düsseldorf, Germany
*
Department of Neurology, Heinrich-Heine-University, Morrenstr. 5, 40225 Düsseldorf, Germany
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Abstract:

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Background:

Controversial data was published about the sodium channel-blocking effect of the endogenous pentapeptide QYNAD, which is elevated in patients with multiple sclerosis and Guillain-Barré-syndrome. In some experiments with single cells and nerve preparations QYNAD inhibited sodium currents to the same extent as the known sodium channel blocker lidocaine whereas in other laboratory testing QYNAD failed to show any effect at all.

Methods:

Micro-electrode arrays with cultured neuronal networks are highly suitable to determine neuroactive activity of applied substances. The impact on electrophysiological parameter changes was compared between QYNAD and the established sodium channel blockers lidocaine and tetrodotoxin (TTX).

Results:

QYNAD did not alter network activity whereas the sodium channel blockers lidocaine (IC50 14.9 µM) and tetrodotoxin (IC50 1.1 nM) reversibly decreased network activity in similar concentrations as in patch-clamp experiments. This decrease of spontaneous electrophysiological activity was achieved by prolonging the interburst-interval.

Conclusion:

Although QYNAD might have mild effects on single-cell sodium currents, there is no significant effect on neuronal network function. These results raise concerns about QYNAD exhibiting a relevant impact on functional disability of the central nervous system in patients.

Résumé:

RÉSUMÉ: Introduction:

Les données publiées sur le blocage des canaux sodiques par le pentapeptide QYNAD, un peptide endogène, sont controversées. Le taux de ce pentapeptide est élevé chez les patients atteints de sclérose en plaques et dans le syndrome de Guillain-Barré. Dans certaines expériences sur des préparations de cellules et de nerfs isolés, le QYNAD inhibe les courants sodiques de façon aussi importante que la lidocaïne, un inhibiteur des canaux sodiques, alors que dans d’autres expériences, il n’a aucun effet.

Méthodes:

Les matrices d’électrodes sont très appropriées pour déterminer la neuroactivité de substances appliquées à des réseaux neuronaux en culture. Nous avons comparé l’impact du QYNAD et de la lidocaïne, un bloquant des canaux sodiques bien connu, et de la tétrodotoxine (TTX) sur les changements de paramètres électrophysiologiques.

Résultats:

Le QYNAD ne modifiait pas l’activité du réseau neuronal alors que la lidocaine, un bloquant des canaux sodiques (IC50 de 14,9 mmol) et la TTX (IC50 de 1,1 nmol) diminuaient de façon réversible l’activité du réseau neuronal à des concentrations semblables à celles utilisées dans les techniques « patch-clamp ». Cette diminution de l’activité électrophysiologique spontanée était obtenue en prolongeant l’intervalle entre les décharges.

Conclusion:

Bien que le QYNAD puisse avoir de légers effets sur les courants sodiques dans un système unicellulaire, il n’a pas d’effet significatif sur la fonction d’un réseau neuronal. Ces résultats soulèvent des doutes quant à l’impact du QYNAD sur l’invalidité fonctionnelle du système nerveux central chez des patients.

Type
Experimental Neurosciences
Information
Canadian Journal of Neurological Sciences , Volume 32 , Issue 3 , August 2005 , pp. 344 - 348
Copyright
Copyright © The Canadian Journal of Neurological 2005

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