Cyclic polypeptide PP-14 modulates the voltage sensitivity of slow sodium channels

© 2016 V. B. Plakhova, I. V. Rogachevsky, Т. N. Shelykh, S. A. Podzorova, B. V. Krylov

Pavlov Institute of Physiology, Russian Academy of Sciences Saint-Petersburg, 199034 Makarova emb., 6

Received 04 Apr 2016

An ability of polypeptide PP-14 to modulate the excitability of nociceptive neuron membrane was investigated by patch- clamp method. The agent was demonstrated to decrease the voltage sensitivity of slow sodium channels NaV1.8, responsible for nociceptive signal coding. Extracellular application of PP-14 induced a significant decrease in the effective charge transfer (Zeff) of the activation gating machinery of NaV1.8 channels, which indicates that the polypeptide may produce analgesia. Nevertheless, the effect of PP-14 is less pronounced as compared to a sharp decrease in nociceptive neuron excitability induced by a more complex molecule of defensin NP-1 applied at subnanomolar concentrations. Quantum- chemical analysis of PP-14 and NP-1 steric structures made it possible to account for the relative efficacy of ligand- receptor binding of these polypeptides.

Key words: nociception, patch-clamp method, slow sodium channels, polypeptides, quantum-chemical calculations

Cite: Plakhova V. B., Rogachevsky I. V., Shelykh Т. N., Podzorova S. A., Krylov B. V.. Tsiklicheskii polipeptid pp-14 moduliruet potentsialochuvstvitelnost medlennykh natrievykh kanalov [Cyclic polypeptide pp-14 modulates the voltage sensitivity of slow sodium channels]. Sensornye sistemy [Sensory systems]. 2016. V. 30(3). P. 234-240 (in Russian).

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