The pentapeptide QYNAD does not inhibit neuronal network activity.
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 micorM) 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.


CONCLUSIONS
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.
Otto
F
F
Department of Neurology, Heinrich-Heine-University Düisseldorf, Germany.
Kieseier
B C
BC
Görtz
P
P
Hartung
H P
HP
Siebler
M
M
D000818:Animals; D015374:Biosensing Techniques; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008012:Lidocaine / Q000494:pharmacology; D008839:Microelectrodes; D009415:Nerve Net / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D009842:Oligopeptides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C450845:pentapeptide QYNAD; D013779:Tetrodotoxin; D008012:Lidocaine