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Quinidine partially blocks mitochondrial voltage-dependent anion channel (VDAC).
Eur Biophys J. 2020 Mar; 49(2):193-205.EB

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.

Authors+Show Affiliations

Department of Biophysics, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India.Department of Biophysics, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India. profsubhendu@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32152682

Citation

Malik, Chetan, and Subhendu Ghosh. "Quinidine Partially Blocks Mitochondrial Voltage-dependent Anion Channel (VDAC)." European Biophysics Journal : EBJ, vol. 49, no. 2, 2020, pp. 193-205.
Malik C, Ghosh S. Quinidine partially blocks mitochondrial voltage-dependent anion channel (VDAC). Eur Biophys J. 2020;49(2):193-205.
Malik, C., & Ghosh, S. (2020). Quinidine partially blocks mitochondrial voltage-dependent anion channel (VDAC). European Biophysics Journal : EBJ, 49(2), 193-205. https://doi.org/10.1007/s00249-020-01426-z
Malik C, Ghosh S. Quinidine Partially Blocks Mitochondrial Voltage-dependent Anion Channel (VDAC). Eur Biophys J. 2020;49(2):193-205. PubMed PMID: 32152682.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quinidine partially blocks mitochondrial voltage-dependent anion channel (VDAC). AU - Malik,Chetan, AU - Ghosh,Subhendu, Y1 - 2020/03/09/ PY - 2019/11/24/received PY - 2020/02/17/accepted PY - 2020/02/12/revised PY - 2020/3/11/pubmed PY - 2020/3/11/medline PY - 2020/3/11/entrez KW - Bilayer electrophysiology KW - Bilayer membrane (BLM) KW - Docking KW - Fluorescence spectroscopy KW - Quinidine KW - Voltage-dependent anion channel (VDAC) SP - 193 EP - 205 JF - European biophysics journal : EBJ JO - Eur. Biophys. J. VL - 49 IS - 2 N2 - 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. SN - 1432-1017 UR - https://www.unboundmedicine.com/medline/citation/32152682/Quinidine_partially_blocks_mitochondrial_voltage-dependent_anion_channel_(VDAC) L2 - https://dx.doi.org/10.1007/s00249-020-01426-z DB - PRIME DP - Unbound Medicine ER -
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