4.6 Article

Hemichannel-mediated release of lactate

期刊

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 36, 期 7, 页码 1202-1211

出版社

SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X15611912

关键词

Astrocytes; connexin; lactate; metabolism; monocarboxylate transporters; pannexin

资金

  1. Wellcome Trust
  2. Moray Endowment Grant
  3. Wellcome Trust ISSF-2 Grant [217SSV]

向作者/读者索取更多资源

In the central nervous system lactate contributes to the extracellular pool of readily available energy substrates and may also function as a signaling molecule which mediates communication between glial cells and neurons. Monocarboxylate transporters are believed to provide the main pathway for lactate transport across the membranes. Here we tested the hypothesis that lactate could also be released via opening of pannexin and/or functional connexin hemichannels. In acute slices prepared from the brainstem, hippocampus, hypothalamus and cortex of adult rats, enzymatic amperometric biosensors detected significant tonic lactate release inhibited by compounds, which block pannexin/connexin hemichannels and facilitated by lowering extracellular [Ca2+] or increased PCO2. Enhanced lactate release triggered by hypoxia was reduced by approximate to 50% by either connexin or monocarboxylate transporter blockers. Stimulation of Schaffer collateral fibers triggered lactate release in CA1 area of the hippocampus, which was facilitated in conditions of low extracellular [Ca2+], markedly reduced by blockade of connexin hemichannels and abolished by lactate dehydrogenase inhibitor oxamate. These results indicate that lactate transport across the membranes may occur via mechanisms other than monocarboxylate transporters. In the central nervous system, hemichannels may function as a conduit of lactate release, and this mechanism is recruited during hypoxia and periods of enhanced neuronal activity.

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