In rat neocortical slices maintained in Mg2+-free Kreb's medium, the effect
s 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 una
ffected. Baclofen, the GABA(B) receptor agonist, produced a concentration-d
ependent depression of discharge frequency, reversibly antagonised by the a
ntagonist (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid (Sch 50911). The EC
50 value for baclofen in 2.4 mM Ca2+ was 11 mu M, 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 mu M, respectivel
y, 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 neocorte
x may be the result of a lower concentration gradient which reinforces the
action of baclofen.