Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2011;6(8):e23020. doi: 10.1371/journal.pone.0023020. Epub 2011 Aug 19.
Two recent reports propose that the depolarizing action of GABA in the immature brain is an artifact of in vitro preparations in which glucose is the only energy source. The authors argue that this does not mimic the physiological environment because the suckling rats use ketone bodies and pyruvate as major sources of metabolic energy. Here, we show that availability of physiologically relevant levels of ketone bodies has no impact on the excitatory action of GABA in immature cultured hippocampal neurons. Addition of β-hydroxybutyrate (BHB), the primary ketone body in the neonate rat, affected neither intracellular calcium elevation nor membrane depolarizations induced by the GABA-A receptor agonist muscimol, when assessed with calcium imaging or perforated patch-clamp recording, respectively. These results confirm that the addition of ketone bodies to the extracellular environment to mimic conditions in the neonatal brain does not reverse the chloride gradient and therefore render GABA hyperpolarizing. Our data are consistent with the existence of a genuine "developmental switch" mechanism in which GABA goes from having a predominantly excitatory role in immature cells to a predominantly inhibitory one in adults.
两篇最近的报告提出，在体外培养物中，GABA 的去极化作用是葡萄糖作为唯一能量来源的人工制品。作者认为，这并不能模拟生理环境，因为哺乳大鼠将酮体和丙酮酸作为主要的代谢能量来源。在这里，我们表明，生理相关水平的酮体的可用性对不成熟培养的海马神经元中 GABA 的兴奋性作用没有影响。添加β-羟丁酸（BHB），即新生大鼠中的主要酮体，在用钙成像或穿孔膜片钳记录分别评估时，均不影响由 GABA-A 受体激动剂 muscimol 诱导的细胞内钙升高或膜去极化。这些结果证实，向细胞外环境中添加酮体以模拟新生儿大脑中的条件并不能逆转氯离子梯度，因此使 GABA 去极化。我们的数据与存在真正的“发育开关”机制一致，在该机制中，GABA 从在不成熟细胞中主要起兴奋作用转变为在成年细胞中主要起抑制作用。
