Responses to GABA^A Receptor Activation Are Altered in NTS Neurons Isolated From Renal-Wrap Hypertensive Rats

The inhibitory amino acid GABA is a potent modulator of the spontaneous discharge and the responses to afferent inputs of neurons in the nucleus of the solitary tract (NTS). To determine if responses to activation of GABA^A receptors are altered in hypertension, GABA^A receptor-evoked whole cell currents were measured in enzymatically dispersed NTS neurons from 33 normotensive (NT, 109±4 mm Hg, n=7) and 24 hypertensive (HT, 167±5 mm Hg, n=24) rats. GABA^A receptor-evoked currents reversed at the calculated equilibrium potential for chloride and were blocked by bicuculline (n=6). Membrane capacitance was the same in neurons from NT (7.5±0.6 pF, n=62) and HT (6.8±0.6 pF, n=51) rats. The EC⁵⁰ for peak GABA-evoked currents cells was significantly greater in neurons from HT (21.0±2.6 μmol/L, n=16) compared with NT rats (13.0±1.8 μmol/L, n=14, P =0.01). The EC⁵⁰ of neurons exhibiting DiA labeling of presumptive aortic nerve terminals was no different than that observed in the nonlabeled cells (19.0±4.9 μmol/L, n=4). The time constant for desensitization of GABA^A-evoked currents was the same in neurons from HT (4.5±0.3 seconds, n=17) and NT rats (3.8±0.3 seconds, n=17, P >0.05). Repetitive pulse application of GABA revealed a more rapid decline in the evoked current in neurons from HT compared with NT rats. The amplitude of the 5th pulse of GABA (5-second duration, 2-second interval) was 21±2% the amplitude of the 1st pulse in NT rats (n=10) and 14±2% in HT rats (n=11, P <0.05). These alterations in GABA^A-receptor evoked currents could render the neurons less sensitive to GABA^A receptor inhibition and influence afferent integration by NTS neurons in HT.