Computational Study of the Loss-of-Function Mutations in the Kv1.5 Channel Associated with Atrial Fibrillation

Atrial fibrillation (AF) is a heart disease caused by defective ion channels in the atria, which affect the action potential (AP) duration and disturb normal heart rhythm. Rapid firing of APs in neighboring atrial cells is a common mechanism of AF, and therefore, therapeutic approaches have focused on extending the AP duration by inhibiting the K⁺ channels involved in repolarization. Of these, Kv1.5 that carries the <i>I</i>_Kur current is a promising target because it is expressed mainly in atria and not in ventricles. In genetic studies of AF patients, both loss-of-function and gain-of-function mutations in Kv1.5 have been identified, indicating that either decreased or increased <i>I</i>_Kur currents could trigger AF. Blocking of already downregulated Kv1.5 channels could cause AF to become chronic. Thus, a molecular-level understanding of how the loss-of-function mutations in Kv1.5 affect <i>I</i>_Kur would be useful for developing new therapeutics. Here, we perform molecular dynamics simulations to study the effect of three loss-of-function mutations in the pore domain of Kv1.5 on ion permeation. Comparison of the pore structures and ion free energies in the wild-type and mutant Kv1.5 channels indicates that conformational changes in the selectivity filter could hinder ion permeation in the mutant channels

Photocatalytic degradation of metronidazole (MNZ) antibiotic by CuO nanoparticles for environmental protection from pharmaceutical pollution

Metronidazole (MNZ) is one of the extensively consumed generic antibiotics, which, due to its high resistance to biological degradation, is considered a potent environmental contaminant. In this study, we use CuO nanoparticles (NPs) for photocatalytic degradation of MNZ. Photocatalytic NPs with a crystallinity of over 80% were synthesized using a facile co-precipitation method followed by calcination at a temperature of 500 °C for a duration of 1 hour. Nanoparticles were characterized thoroughly to investigate their opto-structural properties. We investigated the efficiency of photocatalytic degradation with the variation of MNZ concentration, NP loading and the pH of the MNZ solution. Experimental results revealed that the pH of the MNZ solution strongly controlled the photocatalytic degradation efficiency. As pH was increased from 7 to 11, the degradation rate was enhanced remarkably. Degradation efficiency was also found to be strongly dependent on the concentration of both MNZ solution and CuO NPs.</p