Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Ferreira-Neto, Hildebrando Candido [1, 2] ; Antunes, Vagner R. [1] ; Stern, Javier E. [2]
Total Authors: 3
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil
[2] Georgia Regents Univ, Dept Physiol, Augusta, GA - USA
Total Affiliations: 2
Document type: Journal article
Source: Journal of Neurophysiology; v. 114, n. 1, p. 159-169, JUL 1 2015.
Web of Science Citations: 6

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)

FAPESP's process: 07/04085-0 - Functional analysis of genes contributing to neurogenic hypertension
Grantee:Vagner Roberto Antunes
Support Opportunities: Regular Research Grants
FAPESP's process: 10/05037-1 - Role of purinergic receptors of paraventricular nucleus of the hypothalamus in the neurogenic hypertension
Grantee:Hildebrando Candido Ferreira Neto
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 12/12444-8 - Evaluation of mechanisms of the sinaptic modulation and neuron-glia interaction of purinergic and glutamatergic receptors in the autonomic neurons of the paraventricular nucleus of the hypothalamus
Grantee:Hildebrando Candido Ferreira Neto
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 10/17997-0 - Purinergic mechanisms at the hypothalamus level on sympathetic outflow and its correlation to neurogenic hypertension
Grantee:Vagner Roberto Antunes
Support Opportunities: Regular Research Grants