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

Authors

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

Published in

BMC cardiovascular disorders. Jul 11, 2026. Epub Jul 11, 2026.

Abstract

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.
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 (I_{to, f} current), and transmission electron microscopy (TEM).
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 I_{to, 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.
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.

PMID:
42436362
Bibliographic data and abstract were imported from PubMed on 12 Jul 2026.

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