Inhibition of voltage-gated sodium ion channel by corannulene and computational inversion blockage underlying mechanisms

X Zuo and HQ Yin and XY Li and ZZ Jia and YL Wang and Z Yang and XZ Feng, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 656, 70-77 (2023).

DOI: 10.1016/j.bbrc.2023.03.042

Corannulene (Cor), a special carbon material, evidenced strong protein binding capacity which regulating lysozyme crystallization and controlling reactive oxygen species (ROS) generation. Ion channel protein play role in regulating ion channel functions to affect physiological functions. However, the interaction between Cor and ion channel protein have not been studied. In this study, PEG/Cor nanoparticles (PEG/ Cor Nps) were prepared by mPEG-DSPE. The PEG/Cor Nps localized in cytoplasm and produced cyto-toxicity at high concentration. Whole cell patch clamp examined ion channel functions after incubate PEG/Cor Nps with PC-12 cell. we found that PEG/Cor Nps inhibited voltage-gated Na thorn ion channels in a dose-and time-dependent manner but not act on voltage-gated K thorn ion channels. The potential mech- anisms were revealed by all-atom molecular dynamic (MD) simulations. The results showed that PEG/Cor Nps block the pore of sodium ion channel protein due to dose-and time-dependent accumulation. Besides, the orientation angle (q) configuration of PEG/Cor Nps will be inverted with the accumulation to generate two blocking mechanisms. Different from other carbon nanomaterials, the blockage mechanism of PEG/Cor Nps provides novel insights into the mechanisms of interaction between carbon nano -materials and protein.(c) 2023 Published by Elsevier Inc.

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