Calcium sensing properties of the GABA(B) receptor

The GABA, receptor has been shown to consist of a heterodimer of two relate d 7-transmembrane receptors GABA(B)-R1 and GABA(B)-R2. These receptors shar e close homology to the Ca2+-sensing receptor and also to the metabotropic glutamate receptors, which have also been shown to respond to extracellular calcium. We show here that the GABA(B) receptor also has Ca2+ sensing prop erties. Ca2+ (0.001-1 mM) potentiated the GABA stimulation of [S-35]GTP gam ma S binding in membranes prepared from CHO cells stably expressing the GAB A(B)-R1/R2 heterodimer. The GABA EC,, was reduced from 72 to 7.7 mu M by ad dition of 1 mM Ca2+, with no change in the maximum response. A similar effe ct was observed in membranes from rat brain cortex. Ca2+ also potentiated G ABA inhibition of forskolin-stimulated cAMP levels in the CHO cells and enh anced coupling to GIRK K+ channels in Xenopus oocytes. Other divalent catio ns were ineffective. The effects of Ca2+ were found to be agonist dependent with baclofen having a reduced sensitivity compared to GABA. Calcium appea rs to act allosterically to enhance GABA responses at the GABA(B) receptor, however, unlike the Ca2+-sensing receptor and some of the mGluR family, Ca 2+ does not act as a ligand in its own right. (C) 1999 Elsevier Science Ltd . All rights reserved.