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Publication : Synaptic glutamate release is modulated by the Na+ -driven Cl-/HCO₃⁻ exchanger Slc4a8.

First Author  Sinning A Year  2011
Journal  J Neurosci Volume  31
Issue  20 Pages  7300-11
PubMed ID  21593314 Mgi Jnum  J:173358
Mgi Id  MGI:5013899 Doi  10.1523/JNEUROSCI.0269-11.2011
Citation  Sinning A, et al. (2011) Synaptic glutamate release is modulated by the Na+ -driven Cl-/HCO3- exchanger Slc4a8. J Neurosci 31(20):7300-11
abstractText  On the one hand, neuronal activity can cause changes in pH; on the other hand, changes in pH can modulate neuronal activity. Consequently, the pH of the brain is regulated at various levels. Here we show that steady-state pH and acid extrusion were diminished in cultured hippocampal neurons of mice with a targeted disruption of the Na(+)-driven Cl(-)/HCO(3)(-) exchanger Slc4a8. Because Slc4a8 was found to predominantly localize to presynaptic nerve endings, we hypothesize that Slc4a8 is a key regulator of presynaptic pH. Supporting this hypothesis, spontaneous glutamate release in the CA1 pyramidal layer was reduced but could be rescued by increasing the intracellular pH. The reduced excitability in vitro correlated with an increased seizure threshold in vivo. Together with the altered kinetics of stimulated synaptic vesicle release, these data suggest that Slc4a8 modulates glutamate release in a pH-dependent manner.
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