Liability of a Surgeon for the Extension of an Authorized Operation

Polyunsaturated fatty acids modulate the voltage dependence of several voltage-gated ion channels, thereby being potent modifiers of cellular excitability. Detailed knowledge of this molecular mechanism can be used in designing a new class of small-molecule compounds against hyperexcitability diseases. Here, we show that arginines on one side of the helical K-channel voltage sensor S4 increased the sensitivity to docosahexaenoic acid (DHA), whereas arginines on the opposing side decreased this sensitivity. Glutamates had opposite effects. In addition, a positively charged DHA-like molecule, arachidonyl amine, had opposite effects to the negatively charged DHA. This suggests that S4 rotates to open the channel and that DHA electrostatically affects this rotation. A channel with arginines in positions 356, 359, and 362 was extremely sensitive to DHA: 70 mu M DHA at pH 9.0 increased the current greater than500 times at negative voltages compared with wild type (WT). The small-molecule compound pimaric acid, a novel Shaker channel opener, opened the WT channel. The 356R/359R/362R channel drastically increased this effect, suggesting it to be instrumental in future drug screening

Electronic polymers in lipid membranes

Electrical interfaces between biological cells and man-made electrical devices exist in many forms, but it remains a challenge to bridge the different mechanical and chemical environments of electronic conductors (metals, semiconductors) and biosystems. Here we demonstrate soft electrical interfaces, by integrating the metallic polymer PEDOT-S into lipid membranes. By preparing complexes between alkyl-ammonium salts and PEDOT-S we were able to integrate PEDOT-S into both liposomes and in lipid bilayers on solid surfaces. This is a step towards efficient electronic conduction within lipid membranes. We also demonstrate that the PEDOT-S@alkyl-ammonium:lipid hybrid structures created in this work affect ion channels in the membrane of Xenopus oocytes, which shows the possibility to access and control cell membrane structures with conductive polyelectrolytes

Oxaliplatin neurotoxicity – no general ion channel surface-charge effect

<p>Abstract</p> <p>Background</p> <p>Oxaliplatin is a platinum-based chemotherapeutic drug. Neurotoxicity is the dose-limiting side effect. Previous investigations have reported that acute neurotoxicity could be mediated via voltage-gated ion channels. A possible mechanism for some of the effects is a modification of surface charges around the ion channel, either because of chelation of extracellular Ca²⁺, or because of binding of a charged biotransformation product of oxaliplatin to the channel. To elucidate the molecular mechanism, we investigated the effects of oxaliplatin and its chloride complex [Pt(dach)oxCl]^-on the voltage-gated Shaker K channel expressed in <it>Xenopus </it>oocytes. The recordings were made with the two-electrode and the cut-open oocyte voltage clamp techniques.</p> <p>Conclusion</p> <p>To our surprise, we did not see any effects on the current amplitudes, on the current time courses, or on the voltage dependence of the Shaker wild-type channel. Oxaliplatin is expected to bind to cysteines. Therefore, we explored if there could be a specific effect on single (E418C) and double-cysteine (R362C/F416C) mutated Shaker channels previously shown to be sensitive to cysteine-specific reagents. Neither of these channels were affected by oxaliplatin. The clear lack of effect on the Shaker K channel suggests that oxaliplatin or its monochloro complex has no general surface-charge effect on the channels, as has been suggested before, but rather a specific effect to the channels previously shown to be affected.</p

Joint toxicity of cadmium and ionizing radiation on zooplankton carbon incorporation, growth and mobility

The risk of exposure to radioactive elements is seldom assessed considering mixture toxicity, potentially over- or underestimating biological and ecological effects on ecosystems. This study investigated how three end points, carbon transfer between phytoplankton and Daphnia magna, D. magna mobility and growth, responded to exposure to γ-radiation in combination with the heavy metal cadmium (Cd), using the MIXTOX approach. Observed effects were compared with mixture effects predicted by concentration addition (CA) and independent action (IA) models and with deviations for synergistic/antagonistic (S/A), dose-level (DL), and dose-ratio (DR) dependency interactions. Several patterns of response were observed depending on the end point tested. DL-dependent deviation from the IA model was observed for carbon incorporation with antagonism switching to synergism at higher doses, while the CA model indicated synergism, mainly driven by effects at high doses of γ-radiation. CA detected antagonism regarding acute immobilization, while IA predicted DR-dependency. Both CA and IA also identified antagonism for daphnid growth. In general, effects of combinations of γ-radiation and Cd seem to be antagonistic at lower doses, but synergistic at the higher range of the doses tested. Our results highlight the importance of investigating the effects of exposure to γ-radiation in a multistressor context