Modulation of calcium uptake and D-aspartate release by GABAB receptors in cultured cerebellar granule cells.

(-)Baclofen, a GABAB receptor agonist, and GABA attenuated by 60% the high K+-evoked 45Ca2+ uptake into cultured cerebellar granule cells with an EC50 of 110 +/- 18 nM and 2.4 +/- 0.2 microM, respectively. The attenuation by baclofen of 45Ca2+ uptake was stereospecific and the effect of GABA was unaffected by bicuculline. Moreover, muscimol, a GABAA receptor agonist did not affect the K+-evoked 45Ca2+ uptake. (-)Baclofen and GABA also decreased the K+-evoked and calcium-dependent release of preloaded [3H]D-aspartate from granule cells; however, their potency and efficacy appeared to be less than those for inhibiting the 45Ca2+ uptake. (+)Baclofen and muscimol failed to change this K+-evoked release. The release of [3H]D-aspartate induced by the calcium ionophore A23187 was unaffected by (-)-baclofen. The K+-evoked release of [3H]D-aspartate was effectively inhibited by nimodipine, a voltage sensitive calcium channel blocker. The results suggest that GABAB receptor in cultured cerebellar granule cells plays a crucial role in modulating the uptake of calcium and release of the excitatory transmitter. Moreover, these two effects mediated by GABAB receptor activation may be casually related.