Glycolysis is the primary step for major energy production in the cell. There is strong evidence suggesting that glucose consumption and rate of glycolysis are highly modulated by cytosolic pH The high energy requirement of the mammalian brain is primarily fueled by the degradation of blood-derived glucose. Astrocytes, the major glial cells in the brain, take up a large portion of blood glucose, and by aerobic glycolysis, they preferably produce more lactate (1, 2). Accumulating evidence suggests that astrocytes metabolically support neurons by releasing lactate, which then could be taken up by neighboring neurons (3, 4). Therefore, glucose metabolism in astrocytes was proposed to be modulated by various means of signals presumably originating from neurons (5, 6). It is well documented that astrocytes respond to neuronal activity with an intracellular alkalinization (7-9). Recently, it was shown that the glycolytic rate in astrocytes can be significantly enhanced by an alkaline pH i shift derived from extracellular K ϩ -induced membrane depolarization enhancing bicarbonate uptake via the electrogenic sodium bicarbonate cotransporter NBCe1 (10), which is highly expressed in mouse cortical astrocytes (11). In fact, cytoplasmic pH is well known to be a potential regulator of glucose metabolism, particularly the glycolytic rate, in various cell types (12)(13)(14)(15)
ResultsWe have approached the question whether glucose consumption and glycolysis are stimulated by a fall in [H Ϫ transport into and out of astrocytes, we employed a genetic mouse model with a deletion in the gene for the electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) (21), which is highly expressed in mouse cortical astrocytes (11,22