Functional characterization of the pentapeptide QYNAD on rNav1. 2 channels and its NMR structure

R. Padmashri, K. S. Chakrabarti, D. Sahal, R. Mahalakshmi, S. P. Sarma, S. K. Sikdar

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The endogenous pentapeptide QYNAD (Gln-Tyr-Asn-Ala-Asp) is present in human cerebrospinal fluid (CSF), and its concentration is increased in demyelinating diseases. QYNAD was synthesized and its action on the rNa v1.2 voltage-gated sodium channel α-subunit was studied using whole-cell recordings in a heterologous expression system. The effects were seen only upon equilibration of the peptide in the external bath solution for at least 10 min before the commencement of whole-cell experiments. The steady-state activation curve showed a rightward shift of 10 mV, while the steady-state inactivation curve showed a leftward shift of 5 mV. Frequency-dependent inhibition of the sodium current amplitude was observed at 2-10 Hz, in the presence of external QYNAD, but was not seen when applied internally. Fits of the whole-cell sodium current traces by Hodgkin-Huxley equations revealed subtle changes in the voltage-dependent rate constants governing the transition of the activation and the inactivation gates. Two dimensional NMR spectroscopy revealed the absence of medium and long-range Nuclear Overhauser effects (NOEs), which indicates that the peptide does not adopt any canonical secondary structure in solution. In summary, our studies show that although the pentapeptide QYNAD does not have a defined structure in solution, it has defined actions on the rNav1.2 voltage-gated sodium channel isoform.

Original languageEnglish (US)
Pages (from-to)895-907
Number of pages13
JournalPflugers Archiv European Journal of Physiology
Volume447
Issue number6
DOIs
StatePublished - Mar 2004
Externally publishedYes

Keywords

  • NMR
  • QYNAD
  • Whole-cell recordings
  • rNA1.2 voltage-gated sodium channels

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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