Coles Jonathan A, Martiel Jean-Louis, Laskowska Karolina
GIN, Equipe 5, Université Joseph Fourier, Site Santé de la Merci, F-38706 La Tronche cedex, France.
J Physiol. 2008 Apr 15;586(8):2077-91. doi: 10.1113/jphysiol.2007.148734. Epub 2008 Feb 14.
It has been proposed that glial cells may supply carbon fuel to neurons and also that there are fluxes of ammonium from neurons to glia. We have investigated both these proposals in Apis retinal slices, in which virtually all the mitochondria are in the photoreceptor neurons. Normally the superfusate contained no substrate of energy metabolism; addition of glucose or alanine did not increase oxygen consumption (QO2), confirming that the neurons received adequate substrate from glycogen in the glia. 1,4-Dideoxy-1,4-imino-D-arabinitol (DAB, 100 microm), an inhibitor of glycogen phosphorylase, progressively decreased QO2. This decrease was reversed by alanine but not glucose. Ammonium-sensitive microelectrodes did not detect significant extracellular [NH(4)(+)] (NH(4)(+)) in slices superfused with normal superfusate. Removal of Cl(-), necessary for cotransport of NH(4)(+) into the glia, increased NH(4)(+) so that at the end of 2 min photostimulation mean NH(4)(+) was 0.442 mM (S.E.M. = 0.082 mM, n = 16). In 0 Cl(-), NH(4)(+) was reduced by 2-(methylamino)isobutyrate (MeAIB) an inhibitor of alanine transport. MeAIB also blocked oxidation of alanine in the presence of DAB, but did not decrease QO2 in normal superfusate. Lactate (l and d) and pyruvate (but not glucose) increased QO2 in DAB and decreased NH(4)(+) in 0 Cl(-). These results strengthen the evidence that in superfused retinal slices, glucose is metabolized exclusively in the glia, which supply alanine to the neurons, and that ammonium returns to the glia. They also show that another fuel (perhaps lactate) can be supplied by the glia to the neurons.
有人提出神经胶质细胞可能为神经元提供碳源燃料，并且存在从神经元到神经胶质细胞的铵通量。我们在蜜蜂视网膜切片中研究了这两个提议，在该切片中几乎所有线粒体都存在于光感受器神经元中。正常情况下，灌流液中不含有能量代谢底物；添加葡萄糖或丙氨酸不会增加氧消耗（QO2），这证实了神经元从神经胶质细胞中的糖原获得了充足的底物。1,4-二脱氧-1,4-亚氨基-D-阿拉伯糖醇（DAB，100微摩尔），一种糖原磷酸化酶抑制剂，逐渐降低QO2。这种降低可被丙氨酸逆转，但不能被葡萄糖逆转。铵敏感微电极在灌流正常灌流液的切片中未检测到显著的细胞外[NH(4)(+)]（NH(4)(+)）。去除Cl(-)，这是NH(4)(+)转运到神经胶质细胞所必需的，会增加NH(4)(+)，以至于在2分钟光刺激结束时，平均NH(4)(+)为0.442毫摩尔（标准误=0.082毫摩尔，n=16）。在无Cl(-)条件下，NH(4)(+)被丙氨酸转运抑制剂2-(甲氨基)异丁酸（MeAIB）降低。MeAIB在存在DAB的情况下也会阻断丙氨酸的氧化，但在正常灌流液中不会降低QO2。乳酸（l型和d型）和丙酮酸（但不是葡萄糖）在DAB存在时增加QO2，并在无Cl(-)条件下降低NH(4)(+)。这些结果进一步证明，在灌流的视网膜切片中，葡萄糖仅在神经胶质细胞中代谢，神经胶质细胞向神经元提供丙氨酸，并且铵返回神经胶质细胞。它们还表明神经胶质细胞可以向神经元提供另一种燃料（可能是乳酸）。
