C60 FULLERENES SELECTIVELY INHIBIT BKCa BUT NOT Kv CHANNELS IN PULMONARY ARTERY SMOOTH MUSCLE CELLS

Publication date: Available online 11 April 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Mariia I. Melnyk, Irina V. Ivanova, Dariia O. Dryn, Yuriy I. Prylutskyy, Vasyl V. Hurmach, Maxim Platonov, Lina T. Al Kury, Uwe Ritter, Anatoly I. Soloviev, Alexander V. ZholosAbstractPossessing unique physical and chemical properties, C60 fullerenes are arising as a potential nanotechnological tool that can strongly affect various biological processes. Recent molecular modeling studies have shown that C60 fullerenes can interact with ion channels, but there is lack of data about possible effects of C60 molecule on ion channels expressed in smooth muscle cells (SMC). Here we show both computationally and experimentally that water-soluble pristine C60 fullerene strongly inhibits the large conductance Ca2+-dependent K+ (BKCa), but not voltage-gated K+ (Kv) channels in pulmonary artery SMC. Both molecular docking simulations and analysis of single channel activity indicate that C60 fullerene blocks BKCa channel pore in its open state. In functional tests, C60 fullerene enhanced phenylephrine-induced contraction of pulmonary artery rings by about 25% and reduced endothelium-dependent acetylcholine-induced relaxation by up to 40%. These findings suggest a novel strategy for biomedical application of water-soluble pristine C60 fullerene in vascular dysfunction.Graphical AbstractLarge conductance Ca2+-dependent K+ (BKCa) channels control membrane potential and, in tur...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research