Astrocytic modulation of IKA, NMDA and AMPA currents in NTS neurons of rats is affected by sustained hypoxia

Abstract

Short term sustained hypoxia (SH, FiO2 0.1, 24 h) produces cardiovascular and respiratory changes mainly due to peripheral chemoreflex activation. SH alters the electrophysiological properties of neurons in the NTS, where the first synapses of chemoreflex afferents are located. In the present study we evaluated alterations produced by SH on neuronal excitability and excitatory synaptic transmission in the NTS neurons integral to chemoreflex pathways. After SH protocol, brainstem slices were obtained for electrophysiological recordings using whole cell patch–clamp and fluoracetate (FAC) was used to produce metabolic inhibition of astrocytes. SH increased the action potential discharge in response to positive injected current into NTS neurons (p=0.0048). The presence of A‐type potassium current (IKA) was observed and its peak amplitude was larger in neurons from control [Vm = 10 mV, 1428 ± 600 pA (n=10)] than in SH rats [Vm = 10 mV, 334 ± 76 pA (n=10)]. Inhibition of astrocytes with FAC decreased the IKA amplitude in neurons from control rats [1227 ± 129 pA vs 605 ± 210 pA (n=7)], but not in SH rats [475 ± 110 pA vs 427 ± 114 pA (n=6)]. With respect to excitatory neurotransmission, SH increased AMPA/kainate [−183 ± 122 pA (n=10) vs −353 ± 101 pA (n=10)] and NMDA currents amplitude [61 ± 10 pA (n=7) vs 102 ± 37 pA (n=10)]. Astrocytic modulation on AMPA [aCSF: −353 ± 101 pA vs aCSF + FAC: −369 ± 76 pA, (n=10)] and NMDA currents [aCSF: 102 ± 37 pA vs aCSF + FAC: 108 ± 32 pA, (n=10)] was blunted by SH. In addition, SH increased AMPA current density [control: −6 ± 3.5 pA/pF (n=6) vs SH: −20 ± 12 pA/pF (n=7)]. The data shows that astrocyte modulation of synaptic transmission in NTS neurons integral to the chemoreflex pathways is reduced by SH, which may contribute to the observed increase in the chemoreflex responsiveness on this experimental model.Support or Funding InformationFAPESP, CAPES and CNPq