Retinal pH reflects retinal energy metabolism in the day and night

Retinal pH reflects retinal energy metabolism in the day and night
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DOI:
10.1152/jn.00881.2003
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发表时间:
2004-06-01
影响因子:
2.5
通讯作者:
Mangel, SC
Mangel, SC
中科院分区:
医学3区
文献类型:
--
作者:
Dmitriev, AV;Mangel, SC

文献摘要

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视网膜和大脑其他地方活组织的细胞外pH低于周围环境的pH。我们已经证明,体外视网膜和灌流液之间的pH梯度受昼夜节律(24-h)时钟的调节,因此主观白天的pH梯度小于主观夜晚的pH梯度。我们在这里表明,视网膜pH值的昼夜变化是由伴随着能量产生的H+产生的时钟介导的变化造成的。为了证明这一点,我们抑制了能量代谢,并记录了由此导致的视网膜和超融合液之间的pH差的降低。PH梯度降低的幅度与能量代谢抑制的程度有关。我们还检查了在主观夜晚,昼夜节律诱导的产酸增加是由于能量代谢的增加,还是由于糖酵解的选择性激活,而不是氧化磷酸化。我们发现,选择性抑制氧化磷酸化或糖酵解在主观昼夜中对H+产生的动力学和程度具有几乎相同的影响。因此,糖酵解和氧化磷酸化的比例保持不变,与昼夜节律无关,因此组织和灌流液之间的pH差可以用来评估总的能量产生。我们认为视网膜pH的昼夜节律反映了视网膜能量代谢的昼夜节律。
The extracellular pH of living tissue in the retina and elsewhere in the brain is lower than the pH of the surrounding milieu. We have shown that the pH gradient between the in vitro retina and the superfusion solution is regulated by a circadian (24-h) clock so that it is smaller in the subjective day than in the subjective night. We show here that the circadian changes in retinal pH result from a clock-mediated change in the generation of H+ that accompanies energy production. To demonstrate this, we suppressed energy metabolism and recorded the resultant reduction in the pH difference between the retina and superfusate. The magnitude of the reduction in the pH gradient correlated with the extent of energy metabolism suppression. We also examined whether the circadian-induced increase in acid production during the subjective night results from an increase in energy metabolism or from the selective activation of glycolysis compared with oxidative phosphorylation. We found that the selective suppression of either oxidative phosphorylation or glycolysis had almost identical effects on the dynamics and extent of H+ production during the subjective day and night. Thus the proportion of glycolysis and oxidative phosphorylation is maintained the same regardless of circadian time, and the pH difference between the tissue and superfusion solution can therefore be used to evaluate total energy production. We conclude that circadian clock regulation of retinal pH reflects circadian regulation of retinal energy metabolism.