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 GABAA receptors are altered following exposure to chronic hypoxia, GABAA 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% O2 for 9-12 days. Membrane capacitance was the same in neurons from normoxic (6.9 plus or minus 0.5 pF, n=16) and hypoxic (6.3 plus or minus 0.5 pF, n=15) rats. The EC50 for peak GABA-evoked current density was significantly greater in neurons from hypoxic (21.7 plus or minus 2.2 mu M) compared to normoxic rats (12.2 plus or minus 0.9 mu M) (p0.001). Peak and 5-s adapted GABA currents evoked by 1, 3 and 10 mu M were greater in neurons from normoxic compared to hypoxic rats (p0.05) whereas peak and 5-s adapted responses to 30 and 100 mu M GABA were not different comparing normoxic to hypoxic rats. Desensitization of GABAA-evoked currents was observed at concentrations greater than 3 mu M and, measured as the ratio of the current 5 s after the onset of 100 mu M GABA application to the peak GABA current, was the same in neurons from normoxic (0.37 plus or minus 0.03) and hypoxic rats (0.33 plus or minus 0.04). Reduced sensitivity to GABAA receptor-evoked inhibition in chronic hypoxia could influence chemoreceptor afferent integration by NTS neurons.