Mechanism of action of baclofen in rat dorsal motor nucleus of the vagus

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Abstract

Using whole cell patch-clamp recordings, we investigated the effects of the GABAB receptor agonist baclofen in thin slices of rat brain stem containing identified gastric- or intestinal-projecting dorsal motor nucleus of the vagus (DMV) neurons. Perfusion with baclofen (0.1-100 μM) induced a concentration-dependent outward current (EC50, 3 μM) in 54% of DMV neurons with no apparent differences between gastric- and intestinal-projecting neurons. The outward current was attenuated by pretreatment with the selective GABAB antagonists saclofen and 2-hydroxysaclofen, but not by the synaptic blocker TTX, indicating a direct effect at GABAB receptors on DMV neurons. Using the selective ion channel blockers barium, nifedipine, and apamin, we showed that the outward current was due to effects on potassium and calcium currents as well as calcium-dependent potassium currents. The calcium-mediated components of the outward current were more prominent in intestinal-projecting neurons than in gastric-projecting neurons. These data indicate that although baclofen inhibits both intestinal- and gastric-projecting neurons in the rat DMV, its mechanism of action differs among the neuronal subpopulations.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume280
Issue number6 43-6
StatePublished - Jul 3 2001

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Baclofen
Neurons
Stomach
Calcium
Potassium
GABA-B Receptors
Apamin
Barium
Nifedipine
Ion Channels
Brain Stem
Perfusion

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

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title = "Mechanism of action of baclofen in rat dorsal motor nucleus of the vagus",
abstract = "Using whole cell patch-clamp recordings, we investigated the effects of the GABAB receptor agonist baclofen in thin slices of rat brain stem containing identified gastric- or intestinal-projecting dorsal motor nucleus of the vagus (DMV) neurons. Perfusion with baclofen (0.1-100 μM) induced a concentration-dependent outward current (EC50, 3 μM) in 54{\%} of DMV neurons with no apparent differences between gastric- and intestinal-projecting neurons. The outward current was attenuated by pretreatment with the selective GABAB antagonists saclofen and 2-hydroxysaclofen, but not by the synaptic blocker TTX, indicating a direct effect at GABAB receptors on DMV neurons. Using the selective ion channel blockers barium, nifedipine, and apamin, we showed that the outward current was due to effects on potassium and calcium currents as well as calcium-dependent potassium currents. The calcium-mediated components of the outward current were more prominent in intestinal-projecting neurons than in gastric-projecting neurons. These data indicate that although baclofen inhibits both intestinal- and gastric-projecting neurons in the rat DMV, its mechanism of action differs among the neuronal subpopulations.",
author = "Kirsteen Browning and Travagli, {Renato Alberto}",
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T1 - Mechanism of action of baclofen in rat dorsal motor nucleus of the vagus

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AU - Travagli, Renato Alberto

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N2 - Using whole cell patch-clamp recordings, we investigated the effects of the GABAB receptor agonist baclofen in thin slices of rat brain stem containing identified gastric- or intestinal-projecting dorsal motor nucleus of the vagus (DMV) neurons. Perfusion with baclofen (0.1-100 μM) induced a concentration-dependent outward current (EC50, 3 μM) in 54% of DMV neurons with no apparent differences between gastric- and intestinal-projecting neurons. The outward current was attenuated by pretreatment with the selective GABAB antagonists saclofen and 2-hydroxysaclofen, but not by the synaptic blocker TTX, indicating a direct effect at GABAB receptors on DMV neurons. Using the selective ion channel blockers barium, nifedipine, and apamin, we showed that the outward current was due to effects on potassium and calcium currents as well as calcium-dependent potassium currents. The calcium-mediated components of the outward current were more prominent in intestinal-projecting neurons than in gastric-projecting neurons. These data indicate that although baclofen inhibits both intestinal- and gastric-projecting neurons in the rat DMV, its mechanism of action differs among the neuronal subpopulations.

AB - Using whole cell patch-clamp recordings, we investigated the effects of the GABAB receptor agonist baclofen in thin slices of rat brain stem containing identified gastric- or intestinal-projecting dorsal motor nucleus of the vagus (DMV) neurons. Perfusion with baclofen (0.1-100 μM) induced a concentration-dependent outward current (EC50, 3 μM) in 54% of DMV neurons with no apparent differences between gastric- and intestinal-projecting neurons. The outward current was attenuated by pretreatment with the selective GABAB antagonists saclofen and 2-hydroxysaclofen, but not by the synaptic blocker TTX, indicating a direct effect at GABAB receptors on DMV neurons. Using the selective ion channel blockers barium, nifedipine, and apamin, we showed that the outward current was due to effects on potassium and calcium currents as well as calcium-dependent potassium currents. The calcium-mediated components of the outward current were more prominent in intestinal-projecting neurons than in gastric-projecting neurons. These data indicate that although baclofen inhibits both intestinal- and gastric-projecting neurons in the rat DMV, its mechanism of action differs among the neuronal subpopulations.

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