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

Author(s)

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

Affiliation

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

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

• Document type: Journal article
• Source: Journal of Neurophysiology; v. 114, n. 1, p. 159-169, JUL 1 2015.
• Web of Science Citations: 6

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 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 type: 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 type: Scholarships in Brazil - 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 type: Regular Research Grants
• 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 type: Scholarships abroad - Research Internship - Doctorate