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Thyroid Hormone Diminishes Ca2+ Overload Induced by Hypoxia/Reoxygenation in Cardiomyocytes by Inhibiting Late Sodium Current and Reverse-Na+/Ca2+ Exchange Current.
Pharmacology 2019; :1-10P

Abstract

BACKGROUND AND PURPOSE

Intracellular calcium concentration ([Ca2+]i) overload occurs in myocardial ischemia and -reperfusion. The augmentation of the late sodium current (INaL) causes intracellular Na+ accumulation and subsequent [Ca2+]i overload via the reverse mode of the Na+/Ca2+ exchange current (reverse-INCX), which can lead to arrhythmia and cardiac dysfunction. Thus, inhibition of INaL is a potential therapeutic approach for ischemic heart disease. The aim of this study was to investigate the effects of thyroid hormone on augmented INaL, reverse-INCX, altered action potential duration (APD), and [Ca2+]i concentration in hypoxia/reoxygenation (H/R)-induced ventricular myocytes in vitro.

METHODS

The transient Na+ current (INaT), INaL, reverse-INCX, and APs were recorded using a whole-cell patch-clamp technique in neonatal mouse ventricular myocytes. [Ca2+]i concentration alteration were, respectively, observed by confocal microscopy and flow cytometry.

RESULTS

Triiodothyronine (T3) pretreatment decreased the INaL in a concentration-dependent manner. H/R injury aggravated the INaL, INaT, and reverse-INCX in cardiomyocytes and increased the continuous accumulation of [Ca2+]i (p < 0.05). The application of T3 prior to H/R injury significantly decreased the increased INaL, INaT, and reverse-INCX and blunted the [Ca2+]i increase. Furthermore, T3 pretreatment shortened the APD induced by H/R injury.

CONCLUSION

T3 inhibited H/R-increased INaL and reverse INCX augmentation, shortened the APD, and diminished [Ca2+]i overload, indicating a potential therapeutic use of T3 as an INaL inhibitor to maintain Ca2+ homeostasis and protect cardiomyocytes against H/R injury.

Authors+Show Affiliations

Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan, China, zengbinwhu0272008@163.com.Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan, China.Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan, China.Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan, China.Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31514184

Citation

Zeng, Bin, et al. "Thyroid Hormone Diminishes Ca2+ Overload Induced By Hypoxia/Reoxygenation in Cardiomyocytes By Inhibiting Late Sodium Current and Reverse-Na+/Ca2+ Exchange Current." Pharmacology, 2019, pp. 1-10.
Zeng B, Liao X, Liu L, et al. Thyroid Hormone Diminishes Ca2+ Overload Induced by Hypoxia/Reoxygenation in Cardiomyocytes by Inhibiting Late Sodium Current and Reverse-Na+/Ca2+ Exchange Current. Pharmacology. 2019.
Zeng, B., Liao, X., Liu, L., Ruan, H., & Zhang, C. (2019). Thyroid Hormone Diminishes Ca2+ Overload Induced by Hypoxia/Reoxygenation in Cardiomyocytes by Inhibiting Late Sodium Current and Reverse-Na+/Ca2+ Exchange Current. Pharmacology, pp. 1-10. doi:10.1159/000502804.
Zeng B, et al. Thyroid Hormone Diminishes Ca2+ Overload Induced By Hypoxia/Reoxygenation in Cardiomyocytes By Inhibiting Late Sodium Current and Reverse-Na+/Ca2+ Exchange Current. Pharmacology. 2019 Sep 12;1-10. PubMed PMID: 31514184.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thyroid Hormone Diminishes Ca2+ Overload Induced by Hypoxia/Reoxygenation in Cardiomyocytes by Inhibiting Late Sodium Current and Reverse-Na+/Ca2+ Exchange Current. AU - Zeng,Bin, AU - Liao,Xiaoting, AU - Liu,Lei, AU - Ruan,Huaiyu, AU - Zhang,Caixia, Y1 - 2019/09/12/ PY - 2019/08/07/received PY - 2019/08/18/accepted PY - 2019/9/13/entrez PY - 2019/9/13/pubmed PY - 2019/9/13/medline KW - Action potential duration KW - Calcium overload KW - Hypoxia/reoxygenation KW - Late sodium current KW - Reverse-Na+/Ca2+ exchange current KW - Thyroid hormone KW - Ventricular cardiomyocytes SP - 1 EP - 10 JF - Pharmacology JO - Pharmacology N2 - BACKGROUND AND PURPOSE: Intracellular calcium concentration ([Ca2+]i) overload occurs in myocardial ischemia and -reperfusion. The augmentation of the late sodium current (INaL) causes intracellular Na+ accumulation and subsequent [Ca2+]i overload via the reverse mode of the Na+/Ca2+ exchange current (reverse-INCX), which can lead to arrhythmia and cardiac dysfunction. Thus, inhibition of INaL is a potential therapeutic approach for ischemic heart disease. The aim of this study was to investigate the effects of thyroid hormone on augmented INaL, reverse-INCX, altered action potential duration (APD), and [Ca2+]i concentration in hypoxia/reoxygenation (H/R)-induced ventricular myocytes in vitro. METHODS: The transient Na+ current (INaT), INaL, reverse-INCX, and APs were recorded using a whole-cell patch-clamp technique in neonatal mouse ventricular myocytes. [Ca2+]i concentration alteration were, respectively, observed by confocal microscopy and flow cytometry. RESULTS: Triiodothyronine (T3) pretreatment decreased the INaL in a concentration-dependent manner. H/R injury aggravated the INaL, INaT, and reverse-INCX in cardiomyocytes and increased the continuous accumulation of [Ca2+]i (p < 0.05). The application of T3 prior to H/R injury significantly decreased the increased INaL, INaT, and reverse-INCX and blunted the [Ca2+]i increase. Furthermore, T3 pretreatment shortened the APD induced by H/R injury. CONCLUSION: T3 inhibited H/R-increased INaL and reverse INCX augmentation, shortened the APD, and diminished [Ca2+]i overload, indicating a potential therapeutic use of T3 as an INaL inhibitor to maintain Ca2+ homeostasis and protect cardiomyocytes against H/R injury. SN - 1423-0313 UR - https://www.unboundmedicine.com/medline/citation/31514184/Thyroid_Hormone_Diminishes_Ca2+_Overload_Induced_by_Hypoxia/Reoxygenation_in_Cardiomyocytes_by_Inhibiting_Late_Sodium_Current_and_Reverse-Na+/Ca2+_Exchange_Current L2 - https://www.karger.com?DOI=10.1159/000502804 DB - PRIME DP - Unbound Medicine ER -