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

Abstract Possessing unique physical and chemical properties, C 60 fullerenes are arising as a potential nanotechnological tool that can strongly affect various biological processes. Recent molecular modeling studies have shown that C 60 fullerenes can interact with ion channels, but there is lack of data about possible effects of C 60 molecule on ion channels expressed in smooth muscle cells (SMC). Here we show both computationally and experimentally that water-soluble pristine C 60 fullerene strongly inhibits the large conductance Ca 2+ -dependent K + (BK Ca ), but not voltage-gated K + (K v ) channels in pulmonary artery SMC. Both molecular docking simulations and analysis of single channel activity indicate that C 60 fullerene blocks BK Ca channel pore in its open state. In functional tests, C 60 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 C 60 fullerene in vascular dysfunction.