Endothelin 1 enhances myofilament Ca2+ responsiveness in aequorin-loaded ferret myocardium.
The influence of endothelin 1 on intracellular Ca2+ transients and isometric contractions was investigated in ferret papillary muscles loaded with the Ca(2+)-regulated bioluminescent indicator aequorin. In concentrations of 3 x 10(-9) to 1 x 10(-7) M, endothelin produced dose-dependent increases in the amplitudes of both aequorin light signals (maximum, 31 +/- 12%) and developed tension (maximum, 64 +/- 13%). The peak aequorin light [( Ca2+]i)-peak tension curve generated by increasing endothelin concentrations was steeper and shifted to the left of the curve generated by varying [Ca2+]o; however, the maximum developed tension produced by endothelin did not exceed that produced by 6 mM [Ca2+]o. The effect of endothelin on the amplitude of the aequorin light signal was less than the effect of [Ca2+]o for similar levels of tension development. Moreover, 1 x 10(-7) M endothelin caused an upward shift in the peak aequorin light-peak tension curve generated by varying [Ca2+]o and increased the maximum twitch force by about 12%. The contractions were prolonged, whereas the time course of the Ca2+ transient was not changed in the presence of endothelin. When the function of the sarcoplasmic reticulum was inhibited by 6 microM ryanodine, 10(-7) M endothelin still increased the force generation without increasing the intracellular peak Ca2+, either during isometric twitches or during tetani.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang
J X
JX
Charles A. Dana Research Institute, Harvard Medical School, Boston, Mass.
Paik
G
G
Morgan
J P
JP
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology*; D000331:Aequorin; D000818:Animals; D002046:Bupranolol / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D016232:Endothelins / Q000494:pharmacology* / Q000502:physiology; D005289:Ferrets; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects
D016232:Endothelins; D012433:Ryanodine; D000331:Aequorin; D002046:Bupranolol; D002118:Calcium