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

Gleb Tolstykh, Sergei Belugin, Olga Tolstykh, Steve Wayne Mifflin

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 GABAA receptors are altered in hypertension, GABAA 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. GABAA 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 GABAA-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 GABAA-receptor evoked currents could render the neurons less sensitive to GABAA receptor inhibition and influence afferent integration by NTS neurons in HT.

Original languageEnglish
Pages (from-to)732-736
Number of pages5
JournalHypertension
Volume42
Issue number4
DOIs
StatePublished - 1 Jan 2003

Fingerprint

GABA-A Receptors
Kidney
Neurons
gamma-Aminobutyric Acid
Afferent Neurons
Solitary Nucleus
Bicuculline
Chlorides
Hypertension
Amino Acids
Membranes

Keywords

  • Amino acid
  • Baroreceptors
  • Baroreflex
  • Hypertension, renal
  • Neuroregulators
  • Phosphorylation

Cite this

Tolstykh, Gleb ; Belugin, Sergei ; Tolstykh, Olga ; Mifflin, Steve Wayne. / Responses to GABAA Receptor Activation Are Altered in NTS Neurons Isolated From Renal-Wrap Hypertensive Rats. In: Hypertension. 2003 ; Vol. 42, No. 4. pp. 732-736.
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Responses to GABAA Receptor Activation Are Altered in NTS Neurons Isolated From Renal-Wrap Hypertensive Rats. / Tolstykh, Gleb; Belugin, Sergei; Tolstykh, Olga; Mifflin, Steve Wayne.

In: Hypertension, Vol. 42, No. 4, 01.01.2003, p. 732-736.

Research output: Contribution to journalArticle

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T1 - Responses to GABAA Receptor Activation Are Altered in NTS Neurons Isolated From Renal-Wrap Hypertensive Rats

AU - Tolstykh, Gleb

AU - Belugin, Sergei

AU - Tolstykh, Olga

AU - Mifflin, Steve Wayne

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N2 - 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 GABAA receptors are altered in hypertension, GABAA 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. GABAA 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 GABAA-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 GABAA-receptor evoked currents could render the neurons less sensitive to GABAA receptor inhibition and influence afferent integration by NTS neurons in HT.

AB - 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 GABAA receptors are altered in hypertension, GABAA 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. GABAA 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 GABAA-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 GABAA-receptor evoked currents could render the neurons less sensitive to GABAA receptor inhibition and influence afferent integration by NTS neurons in HT.

KW - Amino acid

KW - Baroreceptors

KW - Baroreflex

KW - Hypertension, renal

KW - Neuroregulators

KW - Phosphorylation

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