title: Hyperpolarization by GABAB receptor agonists in mid-brain periaqueductal gray neurones in vitro.
abstract: 1. The effects of GABAB receptor stimulation on membrane properties of rat periaqueductal gray neurones were studied by use of intracellular recordings from single neurones in superfused brain slices. Intracellular staining with biocytin was used to characterize the anatomical location of each impaled neurone. 2. The GABAB receptor agonist, baclofen, directly hyperpolarized or produced an outward current (single electrode voltage-clamp) in all 66 neurones tested. Baclofen-induced hyperpolarizations were concentration-dependent with an EC50 of approximately 0.6 microM and maximum hyperpolarization with 10 microM baclofen. Hyperpolarizations persisted in the presence of tetrodotoxin (1 microM, n = 2). 3. 2-OH-saclofen, a selective GABAB receptor antagonist, competitively antagonized baclofen-induced hyperpolarizations (n = 4) with equilibrium dissociation constants estimated in two neurones to be 6 and 23 microM. Naloxone (1 microM) did not prevent hyperpolarizations induced by baclofen (n = 34). 4. Hyperpolarizations induced by baclofen were associated with an increased inwardly rectifying potassium conductance. Ba2+ superfusion (5 to 10 mM) blocked this conductance increase (n = 4). Elevation of extracellular potassium concentration (from 2.5 to 6.5 mM) shifted the reversal potential in agreement with predictions of the Nernst equation. 5. Hyperpolarizations produced by baclofen (10 microM) desensitized (> 5% inhibition of the maximum response) in 7/22 neurones during continuous superfusion for 5 min. Strong desensitization (> 25% inhibition of the maximum response) was observed in only 2/22 neurones in the ventrolateral periaqueductal gray. In contrast 6/9 neurones in the laterodorsal tegmental nucleus displayed strong desensitization. 6. These studies demonstrate that baclofen acting on GABAB receptors increases potassium conductance in all lateral and ventrolateral periaqueductal gray neurones.
authors.affiliation: Department of Pharmacology, University of Sydney, NSW, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Chieng
authors.forename: M J
authors.initials: MJ
authors.lastname: Christie
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011188:Potassium / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology; D012680:Sensitivity and Specificity
chemical_list: D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D001418:Baclofen; D011188:Potassium