Post- and presynaptic GABA(B) receptor activation in neonatal rat rostral ventrolateral medulla neurons in vitro

Neuroscience. 1998 Sep;86(1):211-20. doi: 10.1016/s0306-4522(97)00688-x.


Whole-cell patch recordings were made from immature (six- to 12-day-old) rat rostral ventrolateral medulla neurons in brainstem slices. GABA or the specific GABA(B) receptor agonist (-)baclofen (10-50 microM) by superfusion or by pressure ejection induced an outward current or a hyperpolarization, which persisted in a tetrodotoxin (0.3 microM)-containing Krebs' solution in nearly every cell tested. The GABA(B) receptor antagonists 2-hydroxy saclofen (50-200 microM) and CGP 35348 (50-200 microM) dose-dependently suppressed baclofen-currents. Baclofen-currents were suppressed by barium (1 mM) but not by tetraethylammonium (20 mM), low Ca2+ (0.24 mM) solution or in a solution containing the Ca2+ chelator BAPTA-AM (10 microM). The outward current had an estimated reversal potential of -98, -77 and -52 mV in 3.1, 7 and 15 mM [K+]o. Pre-incubation of slices with pertussis toxin (500 microg/ml for 5-7 h) or intracellular dialysis with GDP-beta-S (500 microM) markedly reduced baclofen-currents. Baclofen in low concentrations (1-3 microM) that caused slight or no change of holding currents and of inward or outward currents induced by exogenously applied glutamate or glycine/GABA, decreased excitatory and inhibitory postsynaptic currents by an average of 86.5 +/- 4.3% and 78.4 +/- 2.7%. The GABA(B) antagonist CGP 35348 (100 microM) increased the excitatory postsynaptic currents by an average of 64%, without causing a significant change in holding currents in 10/18 cells tested. Our results indicate the presence of post- and presynaptic GABA(B) receptors in the rostral ventrolateral medulla neurons. Activation of postsynaptic GABA(B) receptors induces an outward K+ current which is barium-sensitive, Ca2+-independent and may be coupled to a pertussis-sensitive G-protein. Activation of presynaptic GABA(B) receptors attenuates excitatory or inhibitory synaptic transmission. More importantly, the observation that CGP 35348 enhanced excitatory synaptic currents implies a removal of tonic activation of presynaptic GABA(B) receptors by endogenously released GABA (disinhibition), supporting the hypothesis that these receptors may have a physiological role in regulating the input and output ratio in a subset of rostral ventrolateral medulla neurons in vivo.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Baclofen / analogs & derivatives
  • Baclofen / pharmacology
  • Calcium / pharmacology
  • Chelating Agents / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Agonists / pharmacology*
  • GABA Antagonists / pharmacology*
  • Guanosine Diphosphate / analogs & derivatives
  • Guanosine Diphosphate / pharmacology
  • In Vitro Techniques
  • Medulla Oblongata / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Organophosphorus Compounds / pharmacology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / drug effects
  • Receptors, GABA-B / physiology*
  • Tetraethylammonium / pharmacology
  • Tetrodotoxin / pharmacology
  • Thionucleotides / pharmacology


  • Chelating Agents
  • GABA Agonists
  • GABA Antagonists
  • Organophosphorus Compounds
  • Receptors, GABA-B
  • Thionucleotides
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Guanosine Diphosphate
  • Tetrodotoxin
  • Egtazic Acid
  • Tetraethylammonium
  • guanosine 5'-O-(2-thiodiphosphate)
  • CGP 35348
  • Baclofen
  • Calcium
  • 2-hydroxysaclofen