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

Padmashri, R. ; Chakrabarti, K. S. ; Sahal, D. ; Mahalakshmi, R. ; Sarma, S. P. ; Sikdar, S. K. (2004) Functional characterization of the pentapeptide QYNAD on rNav1.2 channels and its NMR structure Pflügers Archiv / European Journal of Physiology, 447 (6). pp. 895-907. ISSN 0031-6768

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Official URL: http://www.springerlink.com/content/e0aw338thu9v53...

Related URL: http://dx.doi.org/10.1007/s00424-003-1194-9

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 rNaν1.2 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 rNarNaν1.2 voltage-gated sodium channel isoform.

Item Type:Article
Source:Copyright of this article belongs to Springer.
Keywords:NMR; QYNAD; Rnav1; 2 Voltage-gated Sodium Channels; Whole-cell Recordings
ID Code:84771
Deposited On:27 Feb 2012 13:39
Last Modified:27 Feb 2012 13:39

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