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Alterations in atrial ion channels and tissue structure promote atrial fibrillation in hypothyroid rats

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Abstract

Purpose

It is well known that hyperthyroidism is associated with atrial fibrillation (AF); however, the relationship between hypothyroidism and AF remains controversial.

Methods

Hypothyroidism was established in rats by two methods: methimazole-induced (MMI) and thyroidectomy (TX). MMI model includes control (n = 10), MMI (n = 10), and MMI + L-thyroxine (T4, n = 10). Methimazole was given intragastrically in MMI and MMI + T4 for 12 weeks, and T4 was added intragastrically in MMI + T4 at week 5. TX model includes sham (n = 10), TX (n = 10), and TX + T4 (n = 10). Four weeks after surgery, rats in TX + T4 received T4 for 8 weeks. Triiodothyronine (T3), T4, and thyroid-stimulating hormone (TSH) were measured. Electrophysiology, tissue structure and function, and protein levels of potassium and L-type calcium channels were assessed in the atria.

Results

Severe changes in the atrial structure of hypothyroid rats were observed. Compared with euthyroid rats, atrial effective refractory period (AERP) in hypothyroid rats was significantly shortened; accordingly, inducibility and duration of AF were considerably increased. Protein levels of minK, Kv1.5, Kv4.2, Kv4.3, Kv7.1, and Cav1.2 were upregulated in hypothyroid rats, whereas there was only a tendency toward increased Kir2.1. Kv11.1 was statistically upregulated in the MMI model and had an increasing tendency in the TX model. Conversely, Kir3.1 and Kir3.4 were downregulated in hypothyroid rats. The above changes could be partially inhibited by T4 treatment.

Conclusions

AERP shortening due to altered protein levels of ion channels and atrial structural changes increased the susceptibility to AF in hypothyroidism. Thyroid replacement therapy could prevent electrical and structural remodeling under hypothyroid condition.

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Funding

This study was supported by research grants from National Natural Science Foundation of China (No. 81670297 and No. 81830012).

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Author notes

  1. These authors contributed equally: Jianqiang Li and Zhaorui Liu

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China

    Jianqiang Li, Zhaorui Liu, Hongwei Zhao, Fengxiang Yun, Zhaoguang Liang, Dingyu Wang, Xinbo Zhao, Jiawei Zhang, Hai Cang, Yilun Zou & Yue Li

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  1. Jianqiang Li
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Correspondence to Yue Li.

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The authors declare that they have no conflict of interest.

Ethical approval

This study conformed to the Guide for the Care and Use of Laboratory Animals, published by the US National Institute of Health, and was following the Institutional Guidelines for Animal Care and Use, approved by the Committee on Animal Research of the First Affiliated Hospital of Harbin Medical University.

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Li, J., Liu, Z., Zhao, H. et al. Alterations in atrial ion channels and tissue structure promote atrial fibrillation in hypothyroid rats. Endocrine 65, 338–347 (2019). https://doi.org/10.1007/s12020-019-01968-z

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  • DOI: https://doi.org/10.1007/s12020-019-01968-z

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