Effects of endothelin on intracellular Ca2+ and contractility in single ventricular myocytes from the ferret and human.
We investigated the role of endothelin-1 on peak intracellular Ca2+ ([Ca2+]i) and peak shortening of ventricular myocytes (loaded with indo-1/AM) from failing human hearts. 10 nM of ET-1 significantly increased the cell peak shortening (84 +/- 29%, P less than 0.05) without significantly increasing the peak [Ca2+]i (15 +/- 7%, P greater than 0.05). Further studies on ferret cardiac myocytes indicated that in addition to producing dose-dependent (0.1-10 nM) significant increases in peak shortening (max 55 +/- 6% P less than 0.01) and non-significant increases in peak [Ca2+]i (max 35 +/- 19%, P greater than 0.05), endothelin-1 significantly shifted the peak [Ca2+]i-peak shortening curve upward. The results suggest that endothelin-1 acts directly on human and ferret cardiac myocytes to produce a positive inotropic effect that may predominantly be due to an enhanced myofilament Ca2+ responsiveness.
Qiu
Z
Z
Charles A. Dana Research Institute, Boston, MA.
Wang
J
J
Perreault
C L
CL
Meuse
A J
AJ
Grossman
W
W
Morgan
J P
JP
D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D005289:Ferrets; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D016276:Ventricular Function
D016232:Endothelins; D002118:Calcium