Responses to GABA_A 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% O₂ 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 μM) compared to normoxic rats (12.2±0.9 μM) (p<0.001). Peak and 5-s adapted GABA currents evoked by 1, 3 and 10 μM were greater in neurons from normoxic compared to hypoxic rats (p<0.05) whereas peak and 5-s adapted responses to 30 and 100 μM GABA were not different comparing normoxic to hypoxic rats. Desensitization of GABA _A-evoked currents was observed at concentrations greater than 3 μM and, measured as the ratio of the current 5 s after the onset of 100 μM 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.