Purinergic and vanilloid receptor activation releases glutamate from separate cranial afferent terminals in nucleus tractus solitarius

Young Ho Jin, Timothy W. Bailey, Bai Yan Li, John H. Schild, Michael Andresen

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Vanilloid (VR1) and purinergic (P2X) receptors are found in cranial afferent neurons in nodose ganglia and their central terminations within the solitary tract nucleus (NTS), but little is known about their function. We mechanically dissociated dorsomedial NTS neurons to preserve attached native synapses and tested for VR1 and P2X function primarily in spindle-shaped neurons resembling intact second-order neurons. All neurons (n = 95) exhibited spontaneous glutamate (EPSCs) and GABA (IPSCs)-mediated synaptic currents. VR1 agonist capsaicin (CAP; 100 nM) reversibly increased EPSC frequency, effects blocked by capsazepine. ATP (100 μM) increased EPSC frequency, actions blocked by P2X antagonist pyridoxalphosphate-6-azophenyl-2′, 4′-disulfonic acid (PPADS; 20 μM). In all CAP-resistant neurons, P2X agonist αβ-methylene-ATP (αβ-m-ATP) increased EPSC frequency. Neither CAP nor αβ-m-ATP altered EPSC amplitudes, kinetics, or holding currents. Thus, activation of VR1 and P2X receptors selectively facilitated presynaptic glutamate release on different NTS neurons. PPADS and 2′,3′-O-(2,4,6-trinitrophenyl)-ATP blocked αβ-m-ATP responses, but P2X1-selective antagonist NF023 (8,8′-[carbonylbis (imino-3,1-phenylene carbonylimino)]bis-1,3,5-naphthalenetrisulfonic acid) did not. The pharmacological profile and transient kinetics of ATP responses are consistent with P2X3 homomeric receptors. TTX and Cd2+ did not eliminate agonist-evoked EPSC frequency increases, suggesting that voltage-gated sodium and calcium channels are not required. In nodose ganglia, CAP but not αβ-m-ATP evoked inward currents in slow conducting neurons and the converse pattern in myelinated, rapidly conducting neurons (n = 14). Together, results are consistent with segregation of glutamatergic terminals into either P2X sensitive or VR1 sensitive that correspondingly identify myelinated and unmyelinated afferent pathways at the NTS.

Original languageEnglish (US)
Pages (from-to)4709-4717
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number20
DOIs
StatePublished - May 19 2004

Fingerprint

TRPV Cation Channels
Purinergic Receptors
Solitary Nucleus
Glutamic Acid
Adenosine Triphosphate
Neurons
Nodose Ganglion
Purinergic P2X Receptors
Purinergic P2X3 Receptors
Voltage-Gated Sodium Channels
Afferent Pathways
Afferent Neurons
Acids
Capsaicin
Calcium Channels
Synapses
gamma-Aminobutyric Acid
Pharmacology

Keywords

  • Brain stem
  • Glutamate
  • Presynaptic
  • Purinergic
  • Vanilloid
  • Visceral afferent

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Purinergic and vanilloid receptor activation releases glutamate from separate cranial afferent terminals in nucleus tractus solitarius. / Jin, Young Ho; Bailey, Timothy W.; Li, Bai Yan; Schild, John H.; Andresen, Michael.

In: Journal of Neuroscience, Vol. 24, No. 20, 19.05.2004, p. 4709-4717.

Research output: Contribution to journalArticle

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AU - Jin, Young Ho

AU - Bailey, Timothy W.

AU - Li, Bai Yan

AU - Schild, John H.

AU - Andresen, Michael

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AB - Vanilloid (VR1) and purinergic (P2X) receptors are found in cranial afferent neurons in nodose ganglia and their central terminations within the solitary tract nucleus (NTS), but little is known about their function. We mechanically dissociated dorsomedial NTS neurons to preserve attached native synapses and tested for VR1 and P2X function primarily in spindle-shaped neurons resembling intact second-order neurons. All neurons (n = 95) exhibited spontaneous glutamate (EPSCs) and GABA (IPSCs)-mediated synaptic currents. VR1 agonist capsaicin (CAP; 100 nM) reversibly increased EPSC frequency, effects blocked by capsazepine. ATP (100 μM) increased EPSC frequency, actions blocked by P2X antagonist pyridoxalphosphate-6-azophenyl-2′, 4′-disulfonic acid (PPADS; 20 μM). In all CAP-resistant neurons, P2X agonist αβ-methylene-ATP (αβ-m-ATP) increased EPSC frequency. Neither CAP nor αβ-m-ATP altered EPSC amplitudes, kinetics, or holding currents. Thus, activation of VR1 and P2X receptors selectively facilitated presynaptic glutamate release on different NTS neurons. PPADS and 2′,3′-O-(2,4,6-trinitrophenyl)-ATP blocked αβ-m-ATP responses, but P2X1-selective antagonist NF023 (8,8′-[carbonylbis (imino-3,1-phenylene carbonylimino)]bis-1,3,5-naphthalenetrisulfonic acid) did not. The pharmacological profile and transient kinetics of ATP responses are consistent with P2X3 homomeric receptors. TTX and Cd2+ did not eliminate agonist-evoked EPSC frequency increases, suggesting that voltage-gated sodium and calcium channels are not required. In nodose ganglia, CAP but not αβ-m-ATP evoked inward currents in slow conducting neurons and the converse pattern in myelinated, rapidly conducting neurons (n = 14). Together, results are consistent with segregation of glutamatergic terminals into either P2X sensitive or VR1 sensitive that correspondingly identify myelinated and unmyelinated afferent pathways at the NTS.

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KW - Vanilloid

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