No blocking effects of the pentapeptide QYNAD on Na+ channel subtypes expressed in Xenopus oocytes or action potential conduction in isolated rat sural nerve.
Reversible block of Na(+) channels by endogenous pentapeptide QYNAD has been reported to account for the fast relapses and remissions seen in autoimmune demyelinating disorders. Here it is shown that, in contrast to previous reports, synthetic QYNAD (10-100 microM) applied to Na(+) channels (Na(v)1.6 and 1.8) expressed in Xenopus oocytes was unable to block the peak current or inhibit channel kinetics. Furthermore, QYNAD (100 microM) applied to five isolated rat sural nerve in vitro did not demonstrate any change in the amplitude of compound nerve action potential or latency. The reason for the ineffectiveness of QYNAD has not been elucidated; it was apparently not related to a problem in the synthesis of the pentapeptide. Our experiments raise significant concerns about the suggestion that QYNAD peptide is a Na(+) channel blocker or modulator. However, in a protein library search the amino acid sequence of QYNAD was found to be related to ankyrin-G, which plays a role in Na(+) channel clustering in the node of Ranvier.
Quasthoff
Stefan
S
Department of Neurology, Karl Franzens University, Auenbruggerplatz 22, A-8036 Graz, Austria. stefan.quasthoff@kfunigraz.ac.at
Pojer
Christine
C
Mori
Alexander
A
Hofer
Doris
D
Liebmann
Peter
P
Kieseier
Bernd C
BC
Schreibmayer
Wolfgang
W
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000096:biosynthesis / Q000502:physiology*; D013497:Sural Nerve / Q000187:drug effects* / Q000502:physiology; D014982:Xenopus laevis
D062559:NAV1.8 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; C568319:Scn10a protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C450845:pentapeptide QYNAD