Modulation of Voltage Sensitivity of Slow Sodium Channels by a Synthetic Cyclic Peptide

Effects of a synthetic cyclic peptide on the primary sensory neuron responses are investigated. A decrease in the Na V 1.8 channel voltage sensitivity upon application of the decapeptide Ac–Cys 1 –Leu 2 –Pro 3 –Arg 4 –Glu 5 –Arg 6 –Arg 7 –Ala 8 –Gly 9 –Cys 10 –NH 2 (PIP10) containing a Cys 1 –Cys 10...

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Bibliographic Details
Published in:Human physiology 2021-09, Vol.47 (5), p.564-570
Main Authors: Plakhova, V. B., Rogachevskii, I. V., Penniyaynen, V. A., Podzorova, S. A., Kalinina, A. D., Krylov, B. V., Nozdrachev, A. D.
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Disulfide bonds
Human Physiology
Life Sciences
Neural coding
Pain perception
Peptides
Sensory neurons
Sodium channels (voltage-gated)
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Summary:Effects of a synthetic cyclic peptide on the primary sensory neuron responses are investigated. A decrease in the Na V 1.8 channel voltage sensitivity upon application of the decapeptide Ac–Cys 1 –Leu 2 –Pro 3 –Arg 4 –Glu 5 –Arg 6 –Arg 7 –Ala 8 –Gly 9 –Cys 10 –NH 2 (PIP10) containing a Cys 1 –Cys 10 intramolecular disulfide bridge was demonstrated by the patch-clamp method. The side chains of Arg 4 and Arg 6 residues are sterically unhindered and not involved in strong intramolecular interactions, as shown by the full semiempirical AM1 geometry optimization of the PIP10 molecule. The distance between the central carbon atoms of the guanidinium moieties of these arginine residues is close to 14 Å. According to our hypothesis, it is these positively charged functional groups that are responsible for binding of PIP10 due to intermolecular ion-ionic bonding with negatively charged groups of the Na V 1.8 channel molecule. The agent had no effect on the neurite growth of sensory neurons. The results obtained make it possible to suppose that the PIP10 decapeptide can be used as a safe and effective analgesic medicinal substance, given its capability of specifically modulating the Na V 1.8 channels playing a key role in primary sensory coding in the afferent unit of the nociceptive system.
ISSN:0362-1197
1608-3164
DOI:10.1134/S036211972105008X