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(Hypertension. 2003;42:732.)
© 2003 American Heart Association, Inc.

Scientific Contributions

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

Gleb Tolstykh; Sergei Belugin; Olga Tolstykh; Steve Mifflin

From the University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Correspondence to Steve Mifflin, PhD, Department of Pharmacology, Mail Code 7764, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. E-mail mifflin{at}uthscsa.edu

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.

Key Words: amino acid • baroreceptors • baroreflex • phosphorylation • hypertension, renal • neuroregulators

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