Mechanism of action of baclofen in rat dorsal motor nucleus of the vagus.
Using whole cell patch-clamp recordings, we investigated the effects of the GABA(B) 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 microM) induced a concentration-dependent outward current (EC(50), 3 microM) 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 GABA(B) antagonists saclofen and 2-hydroxysaclofen, but not by the synaptic blocker TTX, indicating a direct effect at GABA(B) 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.
Browning
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Division of Gastroenterology, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109, USA.
Travagli
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology*
D018755:GABA Agonists; D007473:Ion Channels; D018080:Receptors, GABA-B; D001418:Baclofen