pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract

Rafiq Huda, Donald R. McCrimmon, Marco Martina

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The nucleus of the solitary tract (NTS) is the major site for termination of visceral sensory afferents contributing to homeostatic regulation of, for example, arterial pressure, gastric motility, and breathing. Whereas much is known about how different neuronal populations influence these functions, information about the role of glia remains scant. In this article, we propose that glia may contribute to NTS functions by modulating excitatory neurotransmission. We found that acidification (pH 7.0) depolarizes NTS glia by inhibiting K-selective membrane currents. NTS glia also showed functional expression of voltage-sensitive glutamate transporters, suggesting that extracellular acidification regulates synaptic transmission by compromising glial glutamate uptake. To test this hypothesis, we evoked glutamatergic slow excitatory potentials (SEPs) in NTS neurons with repetitive stimulation (20 pulses at 10 Hz) of the solitary tract. This SEP depends on accumulation of glutamate following repetitive stimulation, since it was potentiated by blocking glutamate uptake with DL-threo-fi-ben-zyloxyaspartic acid (TBOA) or a glia-specific glutamate transport blocker, dihydrokainate (DHK). Importantly, extracellular acidification (pH 7.0) also potentiated the SEP. This effect appeared to be mediated through a depolarization-induced inhibition of glial transporter activity, because it was occluded by TBOA and DHK. In agreement, pH 7.0 did not directly alter D-aspartate-induced responses in NTS glia or properties of presynaptic glutamate release. Thus acidification-dependent regulation of glial function affects synaptic transmission within the NTS. These results suggest that glia play a modulatory role in the NTS by integrating local tissue signals (such as pH) with synaptic inputs from peripheral afferents.

Original languageEnglish (US)
Pages (from-to)368-377
Number of pages10
JournalJournal of neurophysiology
Issue number2
StatePublished - Jul 15 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Physiology


  • Astrocyte
  • CNS acid-base influence
  • Glia
  • Glutamate uptake
  • Nucleus of the solitary tract
  • Synaptic transmission
  • TBOA


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