Oxaliplatin neurotoxicity--no general ion channel surface-charge effect.

Journal of Negative Results in Biomedicine
Amir BroomandFredrik Elinder

Abstract

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 Xenopus oocytes. The recordings were made with the two-electrode and the cut-open oocyte voltage clamp techniques. 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 t...Continue Reading

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Citations

Feb 18, 2011·Cancer Chemotherapy and Pharmacology·Susanna B ParkMatthew C Kiernan
Sep 3, 2013·Current Pain and Headache Reports·Jérémy FerrierDavid Balayssac
Jun 1, 2012·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·Mansour S Al MoundhriBadreldin H Ali
Dec 21, 2013·The Journal of Clinical Investigation·Romain CoriatFrédéric Batteux
Jan 27, 2015·Neuroscience Letters·Christopher R Cashman, Ahmet Höke
Aug 30, 2017·World Journal of Clinical Oncology·Ozkan KanatBurcu Caner
Jun 5, 2015·Toxics·Annalisa CantaValentina Alda Carozzi

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