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Background <p>Aluminum oxide nanoparticles (Al₂O₃-NPs) are currently widely applied, although they are known to induce electrocardiographic abnormalities, their crystal phase-dependent effects (including α- and γ-phases) and underlying electrophysiological mechanisms remain unclear.</p> Methods <p>Cardiac injury of α-, γ-, and mix-phase Al₂O₃-NPs was investigated via intraperitoneal injection (100&#xa0;mg/kg) in rats and exposure (20–100&#xa0;µg/mL) in neonatal rat ventricular myocytes (NRVMs). Multidimensional analyses included electrocardiography (ECG), monophasic action potential (MAP) recording, patch-clamp electrophysiology (I<sub>to, f</sub> current), and transmission electron microscopy (TEM).</p> Results <p>α-Al₂O₃-NPs significantly prolonged QT intervals (119.53 ± 9.59 ms, increased by 23.34%; <i>p</i> &lt; 0.001) and elevated arrhythmia scores (2.6 ± 0.6 vs. 0 in controls; <i>p</i> &lt; 0.01), whereas γ-Al₂O₃-NPs showed no such effects. The monophasic action potential duration at 90% repolarization (MAPD₉₀) in the α-Al₂O₃-NPs group was 187.6 ± 4.9 ms, which was significantly increased compared with the control group (<i>p</i> &lt; 0.001). α-Al₂O₃-NPs were found to inhibit I<sub>to, f</sub> current density in a dose-dependent manner, with a significant reduction of 81.8% observed at 100&#xa0;µg/mL (<i>p</i> &lt; 0.001). Ultrastructural damage (myofibril disorganization, mitochondrial cristae fragmentation) and intracellular accumulation of nanoparticles were observed in α-Al₂O₃-NPs group by TEM, with no observed effects for γ-Al₂O₃-NPs.</p> Conclusion <p>Alumina nanoparticles exhibit crystal phase-dependent cardiotoxicity. α-Al₂O₃-NPs induce QT prolongation, MAPD prolongation, ventricular arrhythmias, and ultrastructural damage in rat hearts. In parallel, α-Al₂O₃-NPs suppress Ito, f currents in cultured neonatal rat ventricular myocytes. These findings suggest that Ito, f inhibition may contribute, to the electrophysiological abnormalities induced by α-Al₂O₃-NPs and provide new insights into the potential mechanisms underlying nanoparticle-induced ventricular arrhythmias.</p>

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Alumina nanoparticles-induced reduction in Ito, f contributes to the occurrence of ventricular arrhythmias

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月11日

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  • Haoze Deng,
  • Mengdie Xia,
  • Yiyang Li,
  • Jing Yang,
  • Xiaodong Qian

摘要

Background

Aluminum oxide nanoparticles (Al₂O₃-NPs) are currently widely applied, although they are known to induce electrocardiographic abnormalities, their crystal phase-dependent effects (including α- and γ-phases) and underlying electrophysiological mechanisms remain unclear.

Methods

Cardiac injury of α-, γ-, and mix-phase Al₂O₃-NPs was investigated via intraperitoneal injection (100 mg/kg) in rats and exposure (20–100 µg/mL) in neonatal rat ventricular myocytes (NRVMs). Multidimensional analyses included electrocardiography (ECG), monophasic action potential (MAP) recording, patch-clamp electrophysiology (Ito, f current), and transmission electron microscopy (TEM).

Results

α-Al₂O₃-NPs significantly prolonged QT intervals (119.53 ± 9.59 ms, increased by 23.34%; p < 0.001) and elevated arrhythmia scores (2.6 ± 0.6 vs. 0 in controls; p < 0.01), whereas γ-Al₂O₃-NPs showed no such effects. The monophasic action potential duration at 90% repolarization (MAPD₉₀) in the α-Al₂O₃-NPs group was 187.6 ± 4.9 ms, which was significantly increased compared with the control group (p < 0.001). α-Al₂O₃-NPs were found to inhibit Ito, f current density in a dose-dependent manner, with a significant reduction of 81.8% observed at 100 µg/mL (p < 0.001). Ultrastructural damage (myofibril disorganization, mitochondrial cristae fragmentation) and intracellular accumulation of nanoparticles were observed in α-Al₂O₃-NPs group by TEM, with no observed effects for γ-Al₂O₃-NPs.

Conclusion

Alumina nanoparticles exhibit crystal phase-dependent cardiotoxicity. α-Al₂O₃-NPs induce QT prolongation, MAPD prolongation, ventricular arrhythmias, and ultrastructural damage in rat hearts. In parallel, α-Al₂O₃-NPs suppress Ito, f currents in cultured neonatal rat ventricular myocytes. These findings suggest that Ito, f inhibition may contribute, to the electrophysiological abnormalities induced by α-Al₂O₃-NPs and provide new insights into the potential mechanisms underlying nanoparticle-induced ventricular arrhythmias.