Synaptic glutamate release is modulated by the Na+ -driven Cl-/HCO3â» exchanger Slc4a8.
J Neurosci
; 31(20): 7300-11, 2011 May 18.
Article
em En
| MEDLINE
| ID: mdl-21593314
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sódio
/
Sinapses
/
Ácido Glutâmico
/
Antiportadores de Cloreto-Bicarbonato
/
Simportadores de Sódio-Bicarbonato
Limite:
Animals
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha