ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

Hildebrando Candido Ferreira-Neto, Vagner R. Antunes, Javier E. Stern

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We have previously shown that ATP within the paraventricular nucleus (PVN) induces an increase in sympathetic activity, an effect attenuated by the antagonism of P2 and/or glutamatergic receptors. Here, we evaluated precise cellular mechanisms underlying the ATP-glutamate interaction in the PVN and assessed whether this receptor coupling contributed to osmotically driven sympathetic PVN neuronal activity. Whole-cell patch-clamp recordings obtained from PVN-rostral ventrolateral medulla neurons showed that ATP (100 μM, 1 min, bath applied) induced an increase in firing rate (89%), an effect blocked by kynurenic acid (1 mM) or 4-[[4-Formyl-5-hydroxy-6-methyl-3- [(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid tetrasodium salt (PPADS) (10 μM). Whereas ATP did not affect glutamate synaptic function, +-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor-mediated currents evoked by focal application of AMPA (50 μM, n =13) were increased in magnitude by ATP (AMPA amplitude: 33%, AMPA area: 52%). ATP potentiation of AMPA currents was blocked by PPADS (n =12) and by chelation of intracellular Ca2+ (BAPTA, n =10). Finally, a hyperosmotic stimulus (mannitol 1%, +55 mosM, n =8) potentiated evoked AMPA currents (53%), an effect blocked by PPADS (n =6). Taken together, our data support a functional stimulatory coupling between P2 and AMPA receptors (likely of extrasynaptic location) in PVN sympathetic neurons, which is engaged in response to an acute hyperosmotic stimulus, which might contribute in turn to osmotically driven sympathoexcitatory responses by the PVN.

Original languageEnglish (US)
Pages (from-to)159-169
Number of pages11
JournalJournal of Neurophysiology
Volume114
Issue number1
DOIs
StatePublished - Apr 22 2015

Fingerprint

Paraventricular Hypothalamic Nucleus
Adenosine Triphosphate
Neurons
Glutamic Acid
Kynurenic Acid
Mannitol
propionic acid
bucide
Baths
Salts
pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid

Keywords

  • ATP
  • Hyperosmolarity
  • Paraventricular nucleus
  • Rostral ventrolateral medulla
  • α-amino-3-hydroxy-5-methylisoxazole propionic acid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents. / Ferreira-Neto, Hildebrando Candido; Antunes, Vagner R.; Stern, Javier E.

In: Journal of Neurophysiology, Vol. 114, No. 1, 22.04.2015, p. 159-169.

Research output: Contribution to journalArticle

Ferreira-Neto, Hildebrando Candido ; Antunes, Vagner R. ; Stern, Javier E. / ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents. In: Journal of Neurophysiology. 2015 ; Vol. 114, No. 1. pp. 159-169.
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abstract = "We have previously shown that ATP within the paraventricular nucleus (PVN) induces an increase in sympathetic activity, an effect attenuated by the antagonism of P2 and/or glutamatergic receptors. Here, we evaluated precise cellular mechanisms underlying the ATP-glutamate interaction in the PVN and assessed whether this receptor coupling contributed to osmotically driven sympathetic PVN neuronal activity. Whole-cell patch-clamp recordings obtained from PVN-rostral ventrolateral medulla neurons showed that ATP (100 μM, 1 min, bath applied) induced an increase in firing rate (89{\%}), an effect blocked by kynurenic acid (1 mM) or 4-[[4-Formyl-5-hydroxy-6-methyl-3- [(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid tetrasodium salt (PPADS) (10 μM). Whereas ATP did not affect glutamate synaptic function, +-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor-mediated currents evoked by focal application of AMPA (50 μM, n =13) were increased in magnitude by ATP (AMPA amplitude: 33{\%}, AMPA area: 52{\%}). ATP potentiation of AMPA currents was blocked by PPADS (n =12) and by chelation of intracellular Ca2+ (BAPTA, n =10). Finally, a hyperosmotic stimulus (mannitol 1{\%}, +55 mosM, n =8) potentiated evoked AMPA currents (53{\%}), an effect blocked by PPADS (n =6). Taken together, our data support a functional stimulatory coupling between P2 and AMPA receptors (likely of extrasynaptic location) in PVN sympathetic neurons, which is engaged in response to an acute hyperosmotic stimulus, which might contribute in turn to osmotically driven sympathoexcitatory responses by the PVN.",
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AB - We have previously shown that ATP within the paraventricular nucleus (PVN) induces an increase in sympathetic activity, an effect attenuated by the antagonism of P2 and/or glutamatergic receptors. Here, we evaluated precise cellular mechanisms underlying the ATP-glutamate interaction in the PVN and assessed whether this receptor coupling contributed to osmotically driven sympathetic PVN neuronal activity. Whole-cell patch-clamp recordings obtained from PVN-rostral ventrolateral medulla neurons showed that ATP (100 μM, 1 min, bath applied) induced an increase in firing rate (89%), an effect blocked by kynurenic acid (1 mM) or 4-[[4-Formyl-5-hydroxy-6-methyl-3- [(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid tetrasodium salt (PPADS) (10 μM). Whereas ATP did not affect glutamate synaptic function, +-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor-mediated currents evoked by focal application of AMPA (50 μM, n =13) were increased in magnitude by ATP (AMPA amplitude: 33%, AMPA area: 52%). ATP potentiation of AMPA currents was blocked by PPADS (n =12) and by chelation of intracellular Ca2+ (BAPTA, n =10). Finally, a hyperosmotic stimulus (mannitol 1%, +55 mosM, n =8) potentiated evoked AMPA currents (53%), an effect blocked by PPADS (n =6). Taken together, our data support a functional stimulatory coupling between P2 and AMPA receptors (likely of extrasynaptic location) in PVN sympathetic neurons, which is engaged in response to an acute hyperosmotic stimulus, which might contribute in turn to osmotically driven sympathoexcitatory responses by the PVN.

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