The glycine site on the NMDA receptor of subpostremal NTS neurons

Author(s)

Vander Baptista

• Document type: Doctoral Thesis
• Press: Ribeirão Preto. , gráficos, ilustrações, tabelas.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2004-03-01

Examining board members

Wamberto Antonio Varanda; Antonio Carlos Cassola; Benedito Honório Machado; Wiliam Alves do Prado

• Advisor: Wamberto Antonio Varanda
• Field of knowledge: Biological Sciences - Biophysics
• Indexed in: Banco de Dados Bibliográficos da USP-DEDALUS
• Location: Universidade de São Paulo. Biblioteca Central do Campus de Ribeirão Preto; Baptista, Vander

Abstract

The nucleus of the tractus solitarius (NTS), located in the medulla oblongata, is the first point of synaptic contact for several visceral afferent fibers, including those from the cardiovascular, respiratory and gastrointestinal systems. The subpostremal NTS, the region of the comissural NTS extending from the obex to the posterior tip of the area postrema, plays an important role in the integration of the cardiopulmonary afferent information. Although several neurotransmitter/modulator substances have been identified in the nucleus, glutamatergic, NMDA and non-NMDA, and GABAergic, GABAA, are the main receptors involved in the neurotransmission. The NMDA receptor channel complex needs the binding of two agonists, glutamate and glycine, for its efficient opening. While the glutamate plays the neurotransmitter role, glycine appears to play a more modulatory function depending on its concentration at the synaptic cleft. If the concentration of glycine is higher than the glycine dissociation constant at its site on the NMDA receptor, this site will be saturated and the modulation of the NMDA response by exogenous or synaptically released glycine is not possible. The saturation level of the glycine-binding site varies among different CNS regions and depends fundamentally on (1) expression of the glycine transporters (GLYT1/GLYT2), which can maintain the concentration of glycine in the NMDA synapse at low levels and (2) the type of NMDA receptor subunits. In this work we have investigated the synaptic transmission in the subpostremal NTS and, particularly, if the glycine biding site of the NMDA receptor is saturated or not, so we could infer if glycine could act as a modulator of the NMDA neurotransmission. We have applied the patch clamp technique in brainstem transversal slices of 30-35 days old Wistar rats. The results show that: (1) both the spontaneous postsynaptic currents and those evoked by solitary tract stimulation are due to NMDA, non-NMDA and GABAA receptors activation, (2) The NMDA and non-NMDA receptors are co-localized at the same synaptic site, (3) the NMDA receptors are weakly blocked by Mg2+ at voltages close to the resting membrane potential, suggesting that this receptor can play an important role in synaptic signaling, (4) besides Cl-, another ion, possibly bicarbonate, permeates the channel-receptor GABAA complex and (5) the glycine binding site of the NMDA receptor is not saturated, suggesting that glycine can act as a modulator of the excitatory NMDA transmission in the subpostremal NTS. (AU)