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

Autor(es)

Ferreira-Neto, Hildebrando Candido ^{[1, 2]} ; Antunes, Vagner R. ^[1] ; Stern, Javier E. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Georgia Regents Univ, Dept Physiol, Augusta, GA - USA

• Tipo de documento: Artigo Científico
• Fonte: Journal of Neurophysiology; v. 114, n. 1, p. 159-169, JUL 1 2015.
• Citações Web of Science: 6

Resumo

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 mu M, 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-pyridin yl]azo]-1,3-benzenedisulfonic acid tetrasodium salt (PPADS) (10 mu M). Whereas ATP did not affect glutamate synaptic function, alpha-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor-mediated currents evoked by focal application of AMPA (50 mu M, 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. (AU)

• Processo FAPESP: 07/04085-0 - Análise funcional de genes relacionados à hipertensão neurogênica
• Beneficiário: Vagner Roberto Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/05037-1 - Papel dos receptores purinérgicos do núcleo paraventricular do hipotálamo na hipertensão neurogênica
• Beneficiário: Hildebrando Candido Ferreira Neto
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/12444-8 - Estudo dos mecanismos de modulação sináptica e interação neurônio-glia de receptores purinérgicos e glutamatérgicos em neurônios autônomos do núcleo paraventricular do hipotálamo
• Beneficiário: Hildebrando Candido Ferreira Neto
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 10/17997-0 - Mecanismos da neurotransmissão purinérgica do hipotálamo sobre a atividade autonômica simpática e sua relação com a hipertensão neurogênica
• Beneficiário: Vagner Roberto Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular