Responses to GABAA receptor activation are altered in NTS neurons isolated from chronic hypoxic rats

The inhibitory amino acid GABA is released within the nucleus of the solitary tract (NTS) during hypoxia and modulates the respiratory response to hypoxia. To determine if responses of NTS neurons to activation of GABA(A) receptors are altered following exposure to chronic hypoxia.. GABA(A) receptor-evoked whole cell currents were measured in enzymatically dispersed NTS neurons from normoxic and chronic hypoxic rats. Chronic hypoxic rats were exposed to 10% O-2 for 9-12 days. Membrane capacitance was the same in neurons from normoxic (6.9 +/- 0.5 pF n = 16) and hypoxic (6.3 +/- 0.5 pF, n = 15) rats. The EC50 for peak GABA-evoked current density was significantly greater in neurons from hypoxic (21.7 +/- 2.2 muM) compared to normoxic rats (12.2 +/- 0.9 muM) (p < 0.001). Peak and 5-s adapted GABA currents evoked by 1. 3 and 10 muM were greater in neurons from normoxic compared to hypoxic rats (p < 0.05) whereas peak and 5-s adapted responses to 30 and 100 muM GABA were not different comparing normoxic to hypoxic rats. Desensitization of GABA(A)-evoked currents was observed at concentrations greater than 3 muM and, measured as the ratio of the current 5 s after the onset of 100 muM GABA application to the peak GABA current, was the same in neurons from normoxic (0.37 +/- 0.03) and hypoxic rats (0.33 +/- 0.04). Reduced sensitivity to GABA(A) receptor-evoked inhibition in chronic hypoxia could influence chemoreceptor afferent integration by NTS neurons. (C) 2004 Elsevier B.V. All rights reserved.