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Quinidine partially blocks mitochondrial voltage-dependent anion channel (VDAC)

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Abstract

Quinidine is an antiarrhythmic drug commonly used for the treatment of cardiac ailments. It affects oxidative phosphorylation, calcium uptake, and ion channels of mitochondria. We have investigated the interaction of Quinidine and mitochondrial voltage-dependent anion channel (VDAC). VDAC was purified from neuronal tissue of Wistar rats and in vitro bilayer electrophysiology experiments were performed on it. 50-mM Quinidine treatment on VDAC leads to a sudden drop in its conductance. The dose of Quinidine leading to a half-maximal current through a single-channel VDAC was calculated using Quinidine at different concentrations. In silico molecular docking studies using Autodock-4.2 software indicate interaction between Quinidine and VDAC. Docking results demonstrate the interaction of Quinidine and VDAC on its Glutamic acid residue (Glu-206 of VDAC). Fluorescence spectroscopy results on Quinidine and Glutamic acid interaction show an increase in the intensity and wavelength of Quinidine fluorescence, whereas no interaction between Quinidine and Cysteine was observed. This further supports the Glutamic acid and Quinidine interaction. In conclusion, we report Quinidine partially blocks VDAC due to the interaction of Glutamic acid and Quinidine in the channel pore.

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  1. Department of Biophysics, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India

    Chetan Malik & Subhendu Ghosh

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  1. Chetan Malik
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  2. Subhendu Ghosh
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Appendix

Appendix

(See Fig. 8).

Fig. 8
figure 8

Other energetically less favorable models of interaction between Quinidine and VDAC. Three-dimensional representation of VDAC1 (PubMed ID: 2JK4) secondary structure and Ligand (PubChem ID: 441074) showing the region of interaction site (green dots) at a Tyr198 on the pore wall, b Glu62 and Thr63 externally, c Glu68 and Thr69 on the pore mouth, and d Glu192 on the pore mouth. The points of contact between the ligand and the VDAC have been represented by spheres/green dots

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Malik, C., Ghosh, S. Quinidine partially blocks mitochondrial voltage-dependent anion channel (VDAC). Eur Biophys J 49, 193–205 (2020). https://doi.org/10.1007/s00249-020-01426-z

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