Vesicular neurotransmitter transporter: Bioenergetics and regulation of glutamate transport

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Abstract

Glutamate plays essential roles in chemical transmission as a major excitatory neurotransmitter. The accumulation of glutamate in secretory vesicles is mediated by vesicular glutamate transporters (VGLUTs) that together with the driving electrochemical gradient of proteins influence the subsequent quantum release of glutamate and the function of higher-order neurons. The vesicular content of glutamate is well correlated with membrane potential (Δψ), which suggests that Δψ determines the vesicular glutamate concentration. The transport of glutamate into secretory vesicles is highly dependent on Cl-. This anion stimulates glutamate transport but is inhibitory at higher concentrations. Accumulating evidence indicates that Cl- regulates glutamate transport through control of VGLUT activity and the H+ electrochemical gradient. Recently, a comprehensive study demonstrated that Cl- regulation of VGLUT is competitively inhibited by metabolic intermediates such as ketone bodies. It also showed that ketone bodies are effective in controlling epilepsy. These results suggest a correlation between metabolic state and higher-order brain function. We propose a novel function for Cl- as a fundamental regulator for signal transmission.

Original languageEnglish
Pages (from-to)5558-5565
Number of pages8
JournalBiochemistry
Volume50
Issue number25
DOIs
Publication statusPublished - Jun 28 2011

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ASJC Scopus subject areas

  • Biochemistry

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