在离体大鼠心脏缺血后再灌注时，钠钾ATP酶和钠氢交换体均立即被激活。

Both Na+-K+ ATPase and Na +-H+ exchanger are immediately active upon post-ischemic reperfusion in isolated rat hearts.

作者信息

Van Emous J G, Schreur J H, Ruigrok T J, Van Echteld C J

机构信息

Interuniversity Cardiology Institute of The Netherlands and Department of Cardiology, Heart Lung Institute, University Hospital, Utrecht, The Netherlands.

出版信息

J Mol Cell Cardiol. 1998 Feb;30(2):337-48. doi: 10.1006/jmcc.1997.0597.

DOI:10.1006/jmcc.1997.0597

PMID:9515010

Abstract

Limited time resolution has hampered proper evaluation of changes in intracellular Na+ (Na+i) in whole hearts upon post-ischemic reperfusion. In isolated rat hearts perfused at 37 degrees C, we studied the contribution of the Na+-K+ ATPase and the Na+-H+ exchanger to control of Na+i during reperfusion using 23Na NMR and the shift reagent Tm(DOTP)5- with a time resolution of 5 s. To assess activities of the Na +-K+ ATPase and the Na+-H+ exchanger, 250 micro mol/l ouabain and/or 3 micro mol/l EIPA, respectively, was added to the perfusate during the first 5 min of reperfusion, following 20 min of ischemia. When used, ouabain was also present for 2 min prior to ischemia. Na+i increased during ouabain perfusion prior to ischemia (132+/-5 and 133+/-4% of the pre-ischemic control value after 2 min, in ouabain and ouabain+EIPA hearts, respectively; mean+/-s.e.m.; n=6 per group) resulting in higher end-ischemic values in ouabain and ouabain+EIPA hearts (249+/-9 and 267+/-17% of the pre-ischemic control value, respectively) than in control and EIPA hearts (207+/-21 and 199+/-10% of the pre-ischemic control value, respectively). In ouabain, hearts Na+i started to rise directly upon reperfusion and amounted to 117+/-6% of the end-ischemic value after 60 s of reperfusion. In control hearts, however, Na+i dropped immediately and was 87+/-5% of the end-ischemic value after 60 s, indicating that the Na+-K+ ATPase resumed function directly upon reperfusion. The initial steep increase of Na+i upon reperfusion in ouabain hearts, which diminished after approximately 40 s to the rate of increase observed during ischemia, was absent in ouabain + EIPA hearts. This indicates the existence, although masked by Na+-K+ ATPase activity, of a Na+-H + exchange mediated Na+ influx upon reperfusion. If only EIPA was present during reperfusion the initial decrease in Na+i was faster than in control hearts, corroborating this finding.

摘要

有限的时间分辨率阻碍了对缺血后再灌注时全心内细胞内钠离子（Na⁺i）变化的恰当评估。在37℃灌注的离体大鼠心脏中，我们使用²³Na核磁共振和位移试剂Tm(DOTP)⁵⁻，以5秒的时间分辨率研究了Na⁺-K⁺ ATP酶和Na⁺-H⁺交换体在再灌注期间对Na⁺i控制的作用。为了评估Na⁺-K⁺ ATP酶和Na⁺-H⁺交换体的活性，在缺血20分钟后的再灌注的前5分钟，分别向灌注液中加入250微摩尔/升哇巴因和/或3微摩尔/升EIPA。当使用哇巴因时，在缺血前也存在2分钟。在缺血前灌注哇巴因期间，Na⁺i增加（在哇巴因组和哇巴因+EIPA组中，2分钟后分别为缺血前对照值的132±5%和133±4%；平均值±标准误；每组n = 6），导致哇巴因组和哇巴因+EIPA组的缺血末期值（分别为缺血前对照值的249±9%和267±17%）高于对照组和EIPA组（分别为缺血前对照值的207±21%和199±10%）。在哇巴因组心脏中，再灌注时Na⁺i立即开始上升，再灌注60秒后达到缺血末期值的117±6%。然而，在对照组心脏中，Na⁺i立即下降，60秒后为缺血末期值的87±5%，表明Na⁺-K⁺ ATP酶在再灌注时直接恢复功能。在哇巴因+EIPA组心脏中，没有出现哇巴因组心脏再灌注时Na⁺i最初的急剧增加，这种增加在大约40秒后减弱到缺血期间观察到的增加速率。这表明尽管被Na⁺-K⁺ ATP酶活性掩盖，但在再灌注时存在由Na⁺-H⁺交换介导的Na⁺内流。如果在再灌注期间仅存在EIPA，Na⁺i的最初下降比对照组心脏更快，证实了这一发现。