title: ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents.
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, α-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 Ca(2+) (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.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil; Department of Physiology, Georgia Regents University, Augusta, Georgia.
authors.forename: Hildebrando Candido
authors.initials: HC
authors.lastname: Ferreira-Neto
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil;
authors.forename: Vagner R
authors.initials: VR
authors.lastname: Antunes
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, Georgia jstern@gru.edu.
authors.forename: Javier E
authors.initials: JE
authors.lastname: Stern
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D018048:Receptors, Purinergic P2; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: ATP; hyperosmolarity; paraventricular nucleus; rostral ventrolateral medulla; α-amino-3-hydroxy-5-methylisoxazole propionic acid