title: Functional interaction between charged nanoparticles and cardiac tissue: a new paradigm for cardiac arrhythmia?
abstract: OBJECTIVE
  To investigate the effect of surface charge of therapeutic nanoparticles on sarcolemmal ionic homeostasis and the initiation of arrhythmias.
  
  
  METHODS
  Cultured neonatal rat myocytes were exposed to 50 nm-charged polystyrene latex nanoparticles and examined using a combination of hopping probe scanning ion conductance microscopy, optical recording of action potential characteristics and patch clamp.
  
  
  RESULTS
  Positively charged, amine-modified polystyrene latex nanoparticles showed cytotoxic effects and induced large-scale damage to cardiomyocyte membranes leading to calcium alternans and cell death. By contrast, negatively charged, carboxyl-modified polystyrene latex nanoparticles (NegNPs) were not overtly cytotoxic but triggered formation of 50-250-nm nanopores in the membrane. Cells exposed to NegNPs revealed pro-arrhythmic events, such as delayed afterdepolarizations, reduction in conduction velocity and pathological increment of action potential duration together with an increase in ionic current throughout the membrane, carried by the nanopores.
  
  
  CONCLUSIONS
  The utilization of charged nanoparticles is a novel concept for targeting cardiac excitability. However, this unique nanoscopic investigation reveals an altered electrophysiological substrate, which sensitized the heart cells towards arrhythmias.
authors.affiliation: Myocardial Function Unit, National Heart & Lung Institute, Imperial College London, 4th floor, Imperial Centre for Translational & Experimental Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.|Centre of Excellence for Toxicological Research, exISPESL- INAIL, Dept of Evolution & Functional Biology, Section of Physiology, University of Parma, 43124 Parma, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Miragoli
authors.affiliation: Myocardial Function Unit, National Heart & Lung Institute, Imperial College London, 4th floor, Imperial Centre for Translational & Experimental Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.|Division of Medicine, Imperial College London, Du Cane Road, London, W12 0NN, UK.
authors.forename: Pavel
authors.initials: P
authors.lastname: Novak
authors.affiliation: Lung Cell Biology, Section of Pharmacology & Toxicology, National Heart & Lung Institute, Dovehouse Street, Imperial College London, London, SW3 6LY, UK.
authors.forename: Pakatip
authors.initials: P
authors.lastname: Ruenraroengsak
authors.affiliation: Division of Medicine, Imperial College London, Du Cane Road, London, W12 0NN, UK.|Institute for Life Sciences, University of Southampton 3046, Life Sciences Building 85, Highfield, Southampton, SO17 1BJ, UK.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Shevchuk
authors.affiliation: Division of Medicine, Imperial College London, Du Cane Road, London, W12 0NN, UK.
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Korchev
authors.affiliation: Myocardial Function Unit, National Heart & Lung Institute, Imperial College London, 4th floor, Imperial Centre for Translational & Experimental Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
authors.forename: Max J
authors.initials: MJ
authors.lastname: Lab
authors.affiliation: Lung Cell Biology, Section of Pharmacology & Toxicology, National Heart & Lung Institute, Dovehouse Street, Imperial College London, London, SW3 6LY, UK.
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
authors.affiliation: Myocardial Function Unit, National Heart & Lung Institute, Imperial College London, 4th floor, Imperial Centre for Translational & Experimental Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Gorelik
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002118:Calcium / Q000378:metabolism; D054715:Cardiotoxins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D002478:Cells, Cultured; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D018408:Patch-Clamp Techniques; D051381:Rats
chemical_list: D054715:Cardiotoxins; D002118:Calcium