Effects of Ca2+ concentration on GABA(B) receptor function in rat neocortical slices.
In rat neocortical slices maintained in Mg2+-free Kreb's medium, the effects of Ca2+ concentration on repetitive spontaneous discharges and on GABA(B) receptor-mediated responses were investigated. Over a concentration range of 0.3-2.4 mM Ca2+, there was a reduction of discharge amplitude, with a 50 +/- 6.5% reduction in 0.3 mM Ca2+, whilst the burst frequency remained unaffected. Baclofen, the GABA(B) receptor agonist, produced a concentration-dependent depression of discharge frequency, reversibly antagonised by the antagonist (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid (Sch 50911). The EC50 value for baclofen in 2.4 mM Ca2+ was 11 microM, while the EC50 values in 0.3, 0.6, 1.2, and 1.8 mM Ca2+ were 1.3, 2.5, 3.6, and 10 microM, respectively, resulting in 8.5, 4.4, 3.1, and 1.1-fold leftward shifts. This enhanced action of baclofen in low extracellular Ca2+ concentrations in the neocortex may be the result of a lower concentration gradient which reinforces the action of baclofen.
Department of Anaesthesia and Intensive Care, The University of Adelaide, South Australia, Australia. jong@medicine.adelaide.edu.au
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D018755:GABA Agonists; D018080:Receptors, GABA-B; D001418:Baclofen; D002122:Calcium Chloride