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The pentapeptide QYNAD does not block voltage-gated sodium channels
T R Cummins1, M Renganathan, P K Stys
1Department of Neurology, PVA/EPVA Neuroscience Research Center, Yale University School of Medicine, New Haven, VA Medical Center, West Haven, CT, USA.
Neurology
|January 29, 2003
Summary
The endogenous pentapeptide Gln-Tyr-Asn-Ala-Asp (QYNAD) did not block sodium channels in this study, even at high concentrations. These findings suggest QYNAD may not contribute to demyelinating disease pathophysiology.
Area of Science:
- Neuroscience
- Neurophysiology
- Molecular Biology
Background:
- An endogenous pentapeptide, Gln-Tyr-Asn-Ala-Asp (QYNAD), is found at elevated levels in CSF of patients with demyelinating diseases.
- Previous reports suggested QYNAD blocks voltage-gated sodium channels at low concentrations (10 micro M).
Purpose of the Study:
- To investigate the sensitivity of various sodium channel subtypes to QYNAD.
- To assess QYNAD's potential role in demyelinating disorders, focusing on Na(v)1.6 and Na(v)1.2 channels.
Main Methods:
- Utilized patch-clamp recordings to assay sodium channel function.
- Tested QYNAD in heterologous expression systems and intact neurons, including hippocampal and dorsal root ganglion neurons.
Main Results:
- Synthesized QYNAD failed to block sodium currents even at 500 micro M (50-fold higher than reported).
- QYNAD showed no effect on recombinant Na(v)1.2, Na(v)1.4, Na(v)1.6, Na(v)1.7 channels, or native neuronal sodium currents.
- QYNAD did not impede conduction in the optic nerve, a relevant myelinated pathway in multiple sclerosis.
Conclusions:
- These experiments did not demonstrate any sodium channel blocking effect of QYNAD.
- The proposed role of QYNAD in the pathophysiology of inflammatory neurologic disorders via sodium channel blockade warrants caution.