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

• Published in: Circulation Journal Vol. 73; no. 8; pp. 1504 - 1512
• Main Authors: Suzuki, Shinsuke, Ohkusa, Tomoko, Sato, Takashi, Yoshida, Masaaki, Yasui, Kenji, Miwa, Keiko, Lee, Jong-Kook, Yano, Masafumi, Kodama, Itsuo, Matsuzaki, Masunori
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 2009
• Subjects: Aldosterone; Aldosterone - pharmacology; Animals; Animals, Newborn; Arrhythmias, Cardiac; Cells, Cultured; Connexin 43 - analysis; Connexin 43 - genetics; Connexin43; Dose-Response Relationship, Drug; Electric Conductivity; Gap junction; Gap Junctions - chemistry; Gene Expression Regulation - drug effects; Mineralocorticoid receptor; Mitogen-activated protein kinases (MAPKs); Myocytes, Cardiac - cytology; Rats; RNA, Messenger - analysis
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.CJ-08-1065

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)