Variable effects of endothelin-1 on [Ca2+]i transients, pHi, and contraction in ventricular myocytes.
We examined the effects of endothelin-1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) transients, intracellular pH (pHi), and cell contraction in both embryonic and neonatal as well as in adult ventricular myocytes. Exposure of chick ventricular myocytes to ET-1 (10 nM) significantly decreased both peak systolic and end-diastolic [Ca2+]i (from 949 +/- 43 to 628 +/- 59 nM and from 230 +/- 13 to 162 +/- 8 nM, respectively; P < 0.05, n = 12). The amplitude of cell contraction was also decreased during exposure to 10 nM ET-1 (81.7 +/- 1.2% of control, P < 0.01, n = 12). Exposure to 10 nM ET-1 slightly decreased pHi (-0.055 +/- 0.020 U; P < 0.05). Exposure of cultured neonatal rat ventricular myocytes to ET-1 (10 nM) produced similar effects. Responses of adult rabbit ventricular myocytes to ET-1 were dramatically different from those of embryonic or neonatal ventricular myocytes. Exposure to 10 nM ET-1 increased the amplitude of cell contraction to 159 +/- 32% of control (P < 0.01) without an increase in [Ca2+]i transients. ET-1 also increased pHi (+0.081 +/- 0.047 U; P < 0.01). These results indicate that ET-1 produces a negative inotropic effect by decreasing [Ca2+]i transients and induces a slight intracellular acidosis in immature ventricular myocytes. However, ET-1 causes a positive inotropic effect in adult ventricular myocytes via an intracellular alkalinization, rather than by an increase in the [Ca2+]i transient. Thus the response of myocytes to vasoactive peptides may vary with development and/or species.
Kohmoto
O
O
Faculty of Medicine, University of Tokyo, Japan.
Ikenouchi
H
H
Hirata
Y
Y
Momomura
S
S
Serizawa
T
T
Barry
W H
WH
D000375:Aging / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D002642:Chick Embryo; D016232:Endothelins / Q000494:pharmacology*; D006352:Heart Ventricles; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016232:Endothelins; D000804:Angiotensin II; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium