Modulation of neuronal activity by the endogenous pentapeptide QYNAD.
Inflammation and demyelination both contribute to the neurological deficits characteristic of multiple sclerosis. Neurological dysfunctions are attributable to inflammatory demyelination and, in addition, to soluble factors such as nitric oxide, cytokines and antibodies. QYNAD, an endogenous pentapeptide identified in the cerebrospinal fluid of patients with demyelinating disorders, has been proposed to promote axonal dysfunction by blocking sodium channels. The present study aimed at characterizing the properties of QYNAD in acutely isolated thalamic neurons in vitro. QYNAD, but not a scrambled peptide (NYDQA), blocked sodium channels in neurons by shifting the steady-state inactivation to more negative potentials. Blocking properties followed a dose-response curve with a maximum effect at 10 microm. A fluorescently labelled QYNAD analogue with retained biological activity specifically stained thalamic neurons, positive for type II sodium channels, thus demonstrating the specificity of QYNAD binding. Our study confirms and extends previous observations describing QYNAD as a potent sodium channel-blocking agent. These data as well as our preliminary observations in in vivo experiments in an animal model of inflammatory CNS demyelination warrant further in vivo studies in order to clarify the exact pathogenetic role of QYNAD in inflammatory neurological diseases.
Meuth
Sven G
SG
Institute of Physiology, Otto-von-Guericke University, Magdeburg, Germany.
Budde
Thomas
T
Duyar
Hüseyin
H
Landgraf
Peter
P
Broicher
Tilman
T
Elbs
Martin
M
Brock
Roland
R
Weller
Michael
M
Weissert
Robert
R
Wiendl
Heinz
H
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D005829:Geniculate Bodies / Q000166:cytology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D008564:Membrane Potentials / Q000187:drug effects; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D020318:Rats, Long-Evans; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D000779:Anesthetics, Local; D009842:Oligopeptides; D015222:Sodium Channels; C450845:pentapeptide QYNAD; D013779:Tetrodotoxin