Ames A, Li Y Y, Heher E C, Kimble C R
Neurosurgical Service, Massachusetts General Hospital, Boston 02114.
J Neurosci. 1992 Mar;12(3):840-53. doi: 10.1523/JNEUROSCI.12-03-00840.1992.
Experiments designed to examine the energy requirements of neurophysiological function were performed on isolated rabbit retina. Function was altered by photic stimulation or by function-specific drugs, and the response of energy metabolism was assessed by simultaneous measurements of O2 consumption and lactate production. In other experiments, the supply of O2 or glucose was reduced and the effect on energy metabolism and electrophysiological function was observed. Energy requirements under control conditions in darkness were high, with O2 consumption (per gm dry wt) at 11.3 mumol min-1, with lactate production at 14.8 mumol min-1, and with the derived value for glucose consumption at 9.3 mumol min-1 and for high-energy phosphate (approximately P) generation at 82.6 mumol min-1. Energy reserves were small. Removing glucose abolished the b-wave of the electroretinogram (ERG) with a t1/2 of 1 min, but did not immediately affect O2 consumption or the PIII of the ERG. Removing O2 caused increases of up to 2.7-fold in glycolysis (Pasteur effect) and caused both PIII and b-wave to fail, with a t1/2 of about 5 min. Neurotransmission through the inner retina was supported almost entirely by glycolysis, as evidenced by large increases in lactate production in response to flashing light and decreases in response to transmitter blockers (2.3-fold overall change), with no change in O2 consumption. Phototransduction, on the other hand, was normally supported by oxidative metabolism. The dark current accounted for 41% of the retina's O2 consumption. With O2 reduced, the dark current was partially supported by glycolysis, which accounts (at least in part) for the large Pasteur effect. Na+ transport by NaK ATPase accounted for about half of all energy used, as evidenced by the response to strophanthidin, that is, for 49% of the oxidative energy and 58% of the glycolytic energy. The t1/2 for the turnover of intracellular Na+ was calculated from these data to be less than 1 min. Changes in temperature caused changes in the amplitude of light-evoked electrical responses of 6.5% per degree and caused changes in both O2 consumption and glycolysis of 6.8% per degree (Q10 = 1.9). A surprisingly large fraction of oxidative energy, corresponding to about 40% of the total energy generated, could not be assigned to phototransduction, to neurotransmission, to Na+ transport for other purposes, or to vegetative metabolism. We cannot account for its usage, but it may be related to the (previously reported) rapid turnover of the gamma-phosphate of retinal GTP, the function of which also remains unknown.(ABSTRACT TRUNCATED AT 400 WORDS)
旨在研究神经生理功能能量需求的实验在离体兔视网膜上进行。通过光刺激或功能特异性药物改变视网膜功能，并通过同时测量氧气消耗和乳酸生成来评估能量代谢的反应。在其他实验中，减少氧气或葡萄糖供应，并观察其对能量代谢和电生理功能的影响。在黑暗的对照条件下，能量需求很高，氧气消耗（每克干重）为11.3 μmol·min⁻¹，乳酸生成量为14.8 μmol·min⁻¹，推算出的葡萄糖消耗量为9.3 μmol·min⁻¹，高能磷酸（约P）生成量为82.6 μmol·min⁻¹。能量储备很少。去除葡萄糖后，视网膜电图（ERG）的b波在1分钟的半衰期内消失，但并未立即影响氧气消耗或ERG的PIII波。去除氧气导致糖酵解增加高达2.7倍（巴斯德效应），并使PIII波和b波消失，半衰期约为5分钟。通过内视网膜的神经传递几乎完全由糖酵解支持，这一点可通过对闪光刺激时乳酸生成大幅增加以及对递质阻滞剂反应时乳酸生成减少（总体变化2.3倍）得以证明，而氧气消耗没有变化。另一方面，光转导通常由氧化代谢支持。暗电流占视网膜氧气消耗的41%。在氧气减少时，暗电流部分由糖酵解支持，这（至少部分地）解释了巨大的巴斯德效应。钠钾ATP酶介导的钠转运约占所有能量消耗的一半，对毒毛花苷的反应证明了这一点，即占氧化能量的49%和糖酵解能量的58%。根据这些数据计算出细胞内钠离子周转的半衰期小于1分钟。温度变化导致光诱发电反应幅度每度变化6.5%，并使氧气消耗和糖酵解每度变化6.8%（Q10 = 1.9）。相当大一部分氧化能量，约占总产生能量的40%，无法归因于光转导、神经传递、用于其他目的的钠转运或营养代谢。我们无法解释其用途，但它可能与（先前报道的）视网膜GTP的γ - 磷酸的快速周转有关，其功能也仍然未知。（摘要截选至400字）
