+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

The pentapeptide QYNAD does not block voltage-gated sodium channels

The pentapeptide QYNAD does not block voltage-gated sodium channels

Neurology 60(2): 224-229

Background: An endogenous pentapeptide (Gln-Tyr-Asn-Ala-Asp; QYNAD) that is present at elevated levels in human CSF from patients with demyelinating diseases has been reported to block voltage-gated sodium channels at low (10 muM) concentrations. Objective: Because of the potential importance of sodium channel blocking activity in demyelinating disorders, this study attempted to determine the sensitivity to QYNAD of different sodium channel subtypes, including Nav1.6, the major sodium channel at nodes of Ranvier, and Nav1.2, which is expressed in axons with abnormal myelin. Methods: Sodium channel function was assayed using patch-clamp recordings, both in heterologous expression systems and in intact neurons. Results: QYNAD synthesized in 10 different batches by four different facilities failed to block sodium currents, even at concentrations as high as 500 muM (50-fold higher than the blocking concentration originally reported). QYNAD had no effect on the currents produced by recombinant Nav1.2, Nav1.4, Nav1.6, and Nav1.7 sodium channels or on the sodium currents that are produced by native channels in adult hippocampal or dorsal root ganglion neurons. QYNAD did not interfere with conduction in the optic nerve, a myelinated fiber tract that is often affected in MS. Conclusions: These experiments do not show any sodium channel blocking effect of QYNAD. The conclusion that QYNAD contributes to the pathophysiology of inflammatory neurologic disorders by blocking voltage-gated sodium channels should therefore be viewed with caution.

(PDF emailed within 0-6 h: $19.90)

Accession: 011532032

Download citation: RISBibTeXText

PMID: 12552035

DOI: 10.1212/WNL.60.11.1871-a

Related references

Permeation of large tetra-alkylammonium cations through mutant and wild-type voltage-gated sodium channels as revealed by relief of block at high voltage. Journal of General Physiology 115(4): 435-454, 2000

Block of voltage-gated sodium channels by veratridine in the inner vestibule. Biophysical Journal 84(2 Part 2): 71a-72a, February, 2003

Cloning of a novel voltage gated sodium channel from human cardiac and skeletal muscle evidence for a new gene sub family of voltage gated sodium channels. Biophysical Journal 61(2 PART 2): A108, 1992

Architecture and pore block of eukaryotic voltage-gated sodium channels in view of NavAb bacterial sodium channel structure. Molecular Pharmacology 82(1): 97-104, 2012

State - dependent block of voltage - gated sodium channels by 4 - phenoxyphenylpyrazoles. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 579 6, 2003

Anti-GM1 antibodies can block neuronal voltage-gated sodium channels. Muscle & Nerve 23(9): 1414-1420, September, 2000

Molecular determinants of state-dependent block of voltage-gated sodium channels by pilsicainide. British Journal of Pharmacology 160(6): 1521-1533, 2010

Tri-cyclic antidepressant agents and their metabolites block voltage-gated SCN3A sodium channels. Biophysical Journal 84(2 Part 2): 214a, February, 2003

State-dependent block of rat brain type IIA voltage-gated sodium channels by phenoxyphenyl pyridines. Biophysical Journal 86(1): 117a, January, 2004

Distinct disulfide isomers of μ-conotoxins KIIIA and KIIIB block voltage-gated sodium channels. Biochemistry 51(49): 9826-9835, 2013

State-dependent block of voltage-gated sodium channels by the casein-kinase 1 inhibitor IC261. Investigational New Drugs 35(3): 277-289, 2017

Functional characterization of the pentapeptide QYNAD on rNav1.2 channels and its NMR structure. Pflugers Archiv 447(6): 895-907, 2003

Molecular dissection of lubeluzole use-dependent block of voltage-gated sodium channels discloses new therapeutic potentials. Molecular Pharmacology 83(2): 406-415, 2013

Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine. Journal of Pharmacology and Experimental Therapeutics 326(1): 89-99, 2008

Topical antiseptics for the treatment of sore throat block voltage-gated neuronal sodium channels in a local anaesthetic-like manner. Naunyn-Schmiedeberg's Archives of Pharmacology 380(2): 161-168, 2009