Voltage-gated sodium (NaV) channels are membrane proteins that consist of 24 transmembrane segments organized into four homologous domains, and are essential for action potential generation and propagation. Although the S6 helices of NaV channels line the ion conducting pore and participate in channel activation, their functional architecture is incompletely understood. Our recent studies show ...

NaChBac was the first discovered bacterial sodium voltage-dependent channel, yet computational studies are still limited due to the lack of a crystal structure. In this work, a pore-only construct built using the NavMs template was investigated using unbiased molecular dynamics and metadynamics. The potential of mean force (PMF) from the unbiased run features four minima, three of which corresp...

Several subtypes of voltage-gated Na+ (NaV) channels are important targets for pain management. μ-Conotoxins isolated from venoms of cone snails are potent and specific blockers of different NaV channel isoforms. The inhibitory effect of μ-conotoxins on NaV channels has been examined extensively, but the mechanism of toxin specificity has not been understood in detail. Here the known structure ...

Bisphenol A (BPA) has attracted considerable public attention as it leaches from plastic used in food containers, is detectable in human fluids and recent epidemiologic studies link BPA exposure with diseases including cardiovascular disorders. As heart-toxicity may derive from modified cardiac electrophysiology, we investigated the interaction between BPA and hNav1.5, the predominant voltage-g...

this descriptive study investigates medical students' attitudes toward psychiatric wards. the study was completed at two psychiatric hospitals of shaheed navab safavi, and shaheed ismaily, as well as the psychiatric ward of shaheed rahnamoon hospital. medical students at two level of internship and stagery participated in the study. they completed questionnaires containing general informat...

Voltage-gated sodium channels are targets for many drugs and toxins. However, the rational design of medically relevant channel modulators is hampered by the lack of x-ray structures of eukaryotic channels. Here, we used a homology model based on the x-ray structure of the NavAb prokaryotic sodium channel together with published experimental data to analyze interactions of the μ-conotoxins GIII...

Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the "hinged lid"-based fast inactivation, seen...

BACKGROUND & OBJECTIVES The mechanism of antimony resistance in Leishmania has been studied extensively, in connection with decreased influx and/or increased eflux of the drug. Aquaporin 1 (AQP1) protein has been shown to mediate the uptake of trivalent antimony. This study was aimed to find the expression level of AQP1 gene in resistant versus non-resistant clinical isolates of Leishmania majo...

We present new Brownian dynamics techniques for studying blockers of ion channels. By treating the channel as a fixed body, simulating the blocker molecules using rigid bodies, and using an implicit water force field with explicit ions, we are able to carry out fast simulations that can be used to investigate the dynamics of block and unblock, deduce binding modes, and calculate binding affinit...

normal 0 false false false en-us x-none ar-sa microsoftinternetexplorer4 background : according to beck theory, dysfunctional attitude has a central role in emergence of depression. the aim of this study was to determine contributions of dysfunctional attitude and general health index to depression. methods : in this case-control study, two groups of subjects participated. the first group consi...