Effects of Ca2+ concentration on GABAB receptor function in rat neocortical slices

Abstract

In rat neocortical slices maintained in Mg2+-free Kreb's medium, the effects of Ca2+ concentration on repetitive spontaneous discharges and on GABAB 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 GABAB 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 µM, 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 µM, 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.Key words: baclofen, GABAB receptors, rat neocortical slices, spontaneous discharges, Ca2+ ions, neurotransmitter release.