Is L-lactate a novel signaling molecule in the brain?
In the brain, L-lactate is produced by both neurons and astrocytes. There is no doubt that neurons use L-lactate as a supplementary fuel although the importance of this energy source is disputed. Irrespective of its caloric value, L-lactate might also have a signaling role in the brain. Here, we review several current hypotheses of L-lactate mediated signaling. Some proposed mechanisms require L-lactate entry into the neurons leading to a shift in ATP/ADP ratio or redox state. Others postulate interaction with either known receptor HCA1 (GPR81) or a novel, yet unidentified receptor. We argue that the sensitivity of any such mechanism has to match the concentration range of extracellular L-lactate, which is less than ~1.5 mmol/L under physiologic conditions. From that point of view, some of the proposed mechanisms require supraphysiologic levels of L-lactate and could be engaged during ischemia or seizures when L-lactate concentration rises dramatically. Currently, we do not know whether L-lactate production in the brain occurs in microdomains, which might create higher than average local concentrations. Nevertheless, it is clear that in the brain, as in the peripheral tissues, L-lactate is not only used as a source of energy but also acts as a signaling molecule.
School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
Valentina
V
Mosienko
School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
Anja G
AG
Teschemacher
School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
Sergey
S
Kasparov
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D054086:KATP Channels / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction
C533610:HCAR1 protein, human; D054086:KATP Channels; D043562:Receptors, G-Protein-Coupled; D016194:Receptors, N-Methyl-D-Aspartate; D019344:Lactic Acid; D000255:Adenosine Triphosphate