内皮素-1对心室肌细胞中[Ca2+]i瞬变、细胞内pH值及收缩的可变效应。

Variable effects of endothelin-1 on [Ca2+]i transients, pHi, and contraction in ventricular myocytes.

作者信息

Kohmoto O, Ikenouchi H, Hirata Y, Momomura S, Serizawa T, Barry W H

机构信息

Faculty of Medicine, University of Tokyo, Japan.

出版信息

Am J Physiol. 1993 Sep;265(3 Pt 2):H793-800. doi: 10.1152/ajpheart.1993.265.3.H793.

DOI:10.1152/ajpheart.1993.265.3.H793

PMID:8214112

Abstract

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.

摘要

我们研究了内皮素 -1（ET -1）对胚胎、新生及成年心室肌细胞内游离钙浓度（[Ca2+]i）瞬变、细胞内pH值（pHi）和细胞收缩的影响。将鸡心室肌细胞暴露于ET -1（10 nM）可显著降低收缩期峰值和舒张末期的[Ca2+]i（分别从949±43 nM降至628±59 nM，以及从230±13 nM降至162±8 nM；P<0.05，n = 12）。在暴露于10 nM ET -1期间，细胞收缩幅度也降低（为对照的81.7±1.2%，P<0.01，n = 12）。暴露于10 nM ET -1会使pHi略有降低（-0.055±0.020 U；P<0.05）。将培养的新生大鼠心室肌细胞暴露于ET -1（10 nM）产生了类似的效果。成年兔心室肌细胞对ET -1的反应与胚胎或新生心室肌细胞的反应显著不同。暴露于10 nM ET -1可使细胞收缩幅度增加至对照的159±32%（P<0.01），而[Ca2+]i瞬变并未增加。ET -1还使pHi升高（+0.081±0.047 U；P<0.01）。这些结果表明，ET -1通过降低[Ca2+]i瞬变产生负性变力作用，并在未成熟心室肌细胞中诱导轻微的细胞内酸中毒。然而，ET -1通过细胞内碱化而非[Ca2+]i瞬变增加在成年心室肌细胞中引起正性变力作用。因此，心肌细胞对血管活性肽的反应可能随发育和/或物种而变化。