title: pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract.
abstract: 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-β-benzyloxyaspartic 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.
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. rafiq.huda@gmail.com
authors.forename: Rafiq
authors.initials: R
authors.lastname: Huda
authors.forename: Donald R
authors.initials: DR
authors.lastname: McCrimmon
authors.forename: Marco
authors.initials: M
authors.lastname: Martina
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000502:physiology*; D000818:Animals; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009457:Neuroglia / Q000502:physiology*; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D027322:Amino Acid Transport System X-AG; D011522:Protons
keywords: CNS acid-base influence; TBOA; astrocyte; glia; glutamate uptake; nucleus of the solitary tract; synaptic transmission