GABA B receptor activation protects GABA A receptor from cyclic AMP-dependent down-regulation in rat cerebellar granule cells

Abstract

Interaction between GABA A and GABA B receptors was studied in rat cerebellar granule cells in culture, by the whole-cell patch-clamp approach. Our data show that the GABA B agonist (−)baclofen is not able, per se, to significantly change the muscimol-activated chloride current. However, (−)baclofen dose-dependently prevents the reduction of GABA A receptor function by forskolin, an activator of adenylate cyclase. The effect of baclofen is mediated by a pertussis toxin-sensitive G protein. In fact, in cells treated with pertussis toxin, baclofen and forskolin, the toxin is able to block baclofen action, allowing forskolin to act fully. The protective effect by GABA B receptor activation under these circumstances is most probably related to the prevention of cyclic AMP increases after forskolin treatment. In fact, in these neurons cyclic AMP and protein kinase A activation result in a down-regulation of GABA A receptor function. On the whole, the data indicate the presence of complex modulation of GABA A receptors by GABA B receptor types in cerebellum granule cells.