Gold nanoparticle-spermidine complex blocks the inward rectifier potassium channel

摘要

A previous study showed that negatively charged gold nanoparticles block ion pores by binding to the sulfur group of the cysteine loop of the ion channel when small molecules like amine lead the nanoparticles inside the ion pore. Cells were voltage clamped at -100 mV. Subsequently a bath application of 30 μM Ach produced a current followed by the extracellular application of 100 mM spermidine and 50 nM of nanoparticle complex. Peak amplitude was then recorded. The addition of Ach (30 uM) reversed the effect, and we recorded inhibition of the peak amplitude. We also recorded electrocardiogram (EKG) and the atria effective refractory period (AERP) after treatment with the complex in the atrium of a rabbit heart in a Langendorff apparatus. Upon external application of the complex, the Ach-activated current was blocked by 48.8% ± 3.1% with 82.7% ± 3.1% reversal. In recording the EKG and the AERP after the addition of the complex including 30 mM spermidine with 50 nM nanoparticles, the complete resolution of atrial fibrillation at 50 s and the elongation of AERP from 46 to 52 was observed, which unveils a new class 3 anti arrythmic agent using gold nanoparticles with spermidine. Negatively charged gold nanoparticles (0.8 nm) block ion pores after penetrating the cell membrane with spermidine, thus entering the cells with a polyamine transporter and acting at the intracellular face of the channel via binding to the sulfur group of the human inward rectifying potassium channel- I(KAch).