Effects of aldosterone on Cx43 gap junction expression in neonatal rat cultured cardiomyocytes.
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.


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 approximately 1.5-fold in protein and by approximately 1.2-fold in mRNA). The immunoreactive signal of Cx43 was also increased. Conduction velocity (CV) was increased by approximately 24%. Treatment of the myocytes with aldosterone at higher concentrations (10(-6)-10(-4) mol/L) caused a significant downregulation of Cx43 protein (by approximately 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.
Suzuki
Shinsuke
S
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Ohkusa
Tomoko
T
Sato
Takashi
T
Yoshida
Masaaki
M
Yasui
Kenji
K
Miwa
Keiko
K
Lee
Jong-Kook
JK
Yano
Masafumi
M
Kodama
Itsuo
I
Matsuzaki
Masunori
M
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001145:Arrhythmias, Cardiac; D002478:Cells, Cultured; D018031:Connexin 43 / Q000032:analysis / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D017629:Gap Junctions / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000166:cytology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D018031:Connexin 43; D012333:RNA, Messenger; D000450:Aldosterone