Atp Stimulates Rat Hypothalamic Sympathetic Neurons

نویسندگان

  • Javier E. Stern
  • Vagner R. Antunes
چکیده

42 We have previously shown that ATP within the PVN induces an increase in sympathetic activity; 43 an effect attenuated by the antagonism of P2 and/or glutamatergic receptors. Here, we evaluated 44 precise cellular mechanisms underlying the ATP-glutamate interaction in the PVN, and assessed 45 whether this receptor coupling contributed to osmotically-driven sympathetic PVN neuronal 46 activity. Whole-cell patch clamp recordings obtained from PVN-RVLM neurons showed that 47 ATP (100 μM, 1 min, bath applied) induced an increase in firing rate (89%) an effect blocked by 48 kynurenic acid (1 mM) or PPADS (10 μM). While ATP did not affect glutamate synaptic 49 function, AMPA receptors mediated-currents evoked by focal application of AMPA (50 μM, 50 n=13) were increased in magnitude by ATP (AMPA amplitude: 33%, AMPA area: 52%). ATP 51 potentiation of AMPA currents was blocked by PPADS (n=12) and by chelation of intracellular 52 Ca (BAPTA, n=10). Finally, a hyperosmotic stimulus (mannitol 1%, +55 mOsm, n=8) 53 potentiated evoked AMPA currents (53%), an effect blocked by PPADS (n=6). Taken together, 54 our data support a functional stimulatory coupling between P2 and AMPA receptors (likely of 55 extrasynaptic location) in PVN sympathetic neurons, which is engaged in response to an acute 56 hyperosmotic stimulus, which might contribute in turn to osmotically-driven sympathoexcitatory 57 responses by the PVN. 58

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تاریخ انتشار 2015