细胞内钙离子螯合对常氧和缺氧心脏中去甲肾上腺素释放的影响。

Effects of intracellular Ca2+ chelating on noradrenaline release in normoxic and anoxic hearts.

Du X J, Bobik A, Esler M D, Dart A M

Alfred and Baker Medical Unit, Baker Medical Research Institute, Melbourne, Victoria, Australia.

Clin Exp Pharmacol Physiol. 1997 Nov;24(11):819-23. doi: 10.1111/j.1440-1681.1997.tb02697.x.

Abstract

Ischaemia and anoxia induce excessive noradrenaline (NA) release in the heart by a mechanism independent of both nerve activity and extracellular Ca2+. The present study was designed to examine the potential role of intracellular Ca2+ mobilization in anoxic NA release in the heart by chelating intracellular free Ca2+. 2. In normoxic hearts, preloading with an intracellular free Ca2+ chelator (BAPTA) reduced neuronal NA release by 65%, confirming the effectiveness of the loading protocol. Release of NA independent of nerve activity occurred in hearts subjected to a 40 min period of anoxic, substrate-free and nominal Ca(2+)-free perfusion. Loading hearts with BAPTA prior to anoxia failed to reduce NA overflow (1561 +/- 147 vs 1496 +/- 206 pmol/g over 40 min). Infusion with BAPTA (20 mumol/L) during the first 25 min of the anoxic period reduced the quantity of anoxic NA release by approximately 25% from 2013 +/- 124 to 1476 +/- 207 pmol/g (P < 0.05). 3. Our results confirm that anoxic NA release is predominantly a Ca(2+)-independent process with Ca2+ mobilization from endogenous storage playing only a minor contributing role.

摘要

缺血和缺氧通过一种独立于神经活动和细胞外Ca2+的机制诱导心脏中去甲肾上腺素（NA）过度释放。本研究旨在通过螯合细胞内游离Ca2+来研究细胞内Ca2+动员在心脏缺氧性NA释放中的潜在作用。2. 在正常氧合的心脏中，用细胞内游离Ca2+螯合剂（BAPTA）预加载可使神经元NA释放减少65%，证实了加载方案的有效性。在进行40分钟缺氧、无底物和名义上无Ca(2+)灌注的心脏中，发生了独立于神经活动的NA释放。在缺氧前用BAPTA加载心脏未能减少NA溢出（40分钟内为1561±147对1496±206 pmol/g）。在缺氧期的前25分钟内输注BAPTA（20 μmol/L）可使缺氧性NA释放量从2013±124降至1476±207 pmol/g，减少约25%（P<0.05）。3. 我们的结果证实，缺氧性NA释放主要是一个不依赖Ca(2+)的过程，内源性储存的Ca2+动员仅起次要作用。