Effects of Aldosterone on Cx43 Gap Junction Expression in Neonatal Rat Cultured Cardiomyocytes

Shinsuke Suzuki; Tomoko Ohkusa; Takashi Sato; Masaaki Yoshida; Kenji Yasui; Keiko Miwa; Jong-Kook Lee; Masafumi Yano; Itsuo Kodama; Masunori Matsuzaki

doi:10.1253/circj.CJ-08-1065

Molecular Cardiology

Effects of Aldosterone on Cx43 Gap Junction Expression in Neonatal Rat Cultured Cardiomyocytes

Shinsuke Suzuki, Tomoko Ohkusa, Takashi Sato, Masaaki Yoshida, Kenji Yasui, Keiko Miwa, Jong-Kook Lee, Masafumi Yano, Itsuo Kodama, Masunori Matsuzaki

Author information

Shinsuke Suzuki
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine
Tomoko Ohkusa
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine
Takashi Sato
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine
Masaaki Yoshida
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine
Kenji Yasui
Department of Bioinformation Analysis, Research Institute of Environmental Medicine, Nagoya University
Keiko Miwa
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University
Jong-Kook Lee
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University
Masafumi Yano
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine
Itsuo Kodama
Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University
Masunori Matsuzaki
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine

Keywords: Aldosterone, Connexin43, Gap junction, Mineralocorticoid receptor, Mitogen-activated protein kinases (MAPKs)

JOURNAL FREE ACCESS

2009 Volume 73 Issue 8 Pages 1504-1512

DOI https://doi.org/10.1253/circj.CJ-08-1065

View "Advance Publication" version (June 16, 2009).

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Abstract

Background: The renin-angiotensin-aldosterone system affects cellular morphology and function in the heart under a variety of pathologic conditions. In the present study the effects of aldosterone on the expression of connexin (Cx) 43 gap junctions in cardiomyocytes were investigated. Methods and Results: Cultured rat ventricular myocytes were exposed to aldosterone for 24 h. The protein and mRNA expression of Cx43 was estimated. Propagation of excitation was visualized by a multiple electrode array system. Treatment of the myocytes with 10^-8 mol/L aldosterone resulted in a significant upregulation of Cx43 (by ~1.5-fold in protein and by ~1.2-fold in mRNA). The immunoreactive signal of Cx43 was also increased. Conduction velocity (CV) was increased by ~24%. Treatment of the myocytes with aldosterone at higher concentrations (10^-6-10^-4 mol/L) caused a significant downregulation of Cx43 protein (by ~0.3-fold) without affecting Cx43 mRNA levels, and decreased the CV by ~23%. The Cx43 upregulation and CV acceleration at 10^-8 mol/L aldosterone were prevented by pretreatment with eplerenone, but unaffected by mifepristone. Pretreatment of the myocytes with eplerenone or mifepristone did not prevent the Cx43 downregulation by aldosterone at 10^-6-10^-4 mol/L. Conclusions: Aldosterone may be involved in arrhythmogenic gap junction remodeling through its dual effects on the expression of Cx43. (Circ J 2009; 73: 1504 - 1512)

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