Key result
Negatively charged nanoparticles triggered the formation of nanopores in cardiomyocyte membranes, leading to pro-arrhythmic events including a prolongation of action potential duration from 174 ms to 430 ms.
Why the study?
Does exposure to charged nanoparticles induce pro-arrhythmic events and alter sarcolemmal ionic homeostasis in cultured neonatal rat myocytes?
Does exposure to charged nanoparticles induce pro-arrhythmic events and alter sarcolemmal ionic homeostasis in cultured neonatal rat myocytes?
Charged nanoparticles alter the electrophysiological substrate of cardiomyocytes, sensitizing them to arrhythmias and demonstrating potential cytotoxicity depending on surface charge.
Answers are grounded in this paper and cite their sources.
Alerts to arrhythmogenic risks of charged nanoparticles in cardiac nanomedicine; hypothesis-generating and requires in vivo confirmation.
AIM: To investigate the effect of surface charge of therapeutic nanoparticles on sarcolemmal ionic homeostasis and the initiation of arrhythmias. MATERIALS & 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. CONCLUSION: 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.
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Miragoli et al. (2012) studied Cardiac arrhythmia. Charged polystyrene latex nanoparticles (positive and negative) vs. Unexposed control cells was evaluated on Action potential duration (APD90). Negatively charged nanoparticles triggered the formation of nanopores in cardiomyocyte membranes, leading to pro-arrhythmic events including a prolongation of action potential duration from 174 ms to 430 ms.
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