Modulation of Ca2+ transients in neonatal and adult rat cardiomyocytes by endothelin-1.
Endothelin-1 (ET-1) may exert inotropic and chronotropic effects in cardiac muscle by modulating intracellular Ca2+. This study assesses effects of ET-1 on intracellular free Ca2+ concentration ([Ca2+]i) in neonatal and adult rat cardiomyocytes. [Ca2+]i was measured by Fura 2 methodology. ET receptor subtypes were determined by binding studies. ET-1 increased neonatal and adult [Ca2+]i and spike frequency in a dose-dependent manner. It decreased [Ca2+]i amplitude in neonatal cardiomyocytes but had no effect on [Ca2+]i amplitude in adult cells. The ET(A) receptor antagonist BQ-123 reduced ET-1-induced responses and the ETB receptor agonist IRL-1620 increased [Ca2+]i. ET-1 binding studies demonstrated 85% displacement by BQ-123 and 15% by the ETB receptor agonist sarafotoxin S6c, suggesting a predominance of ET(A) receptors. These data demonstrate that in neonatal and adult cardiomyocytes ET-1 has stimulatory effects on [Ca2+]i which are mediated predominantly via ET(A) receptors. Therefore, ET-1 may influence cardiac development and function.
Touyz
R M
RM
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Québec, Canada.
Fareh
J
J
Thibault
G
G
Larivière
R
R
Schiffrin
E L
EL
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium