Developmental profile and mechanisms of GABA-induced calcium signaling in hippocampal astrocytes

GABA (gamma-aminobutyric acid) is a transmitter with dual action. Whereas it excites neurons during the first week of postnatal development, it represents the major inhibitory transmitter in the mature brain. GABA also activates astrocytes by binding to ionotropic (GABA(A)) and metabotropic (GABA(B)) receptors. This results in glial calcium transients which can induce the release of gliotransmitters, rendering GABA an important mediator of neuron-glia interaction. Using whole-cell patch-clamp and ratiometric calcium imaging in hippocampal slices from rats at postnatal days 3-34, we have analyzed the developmental profile as well as the cellular mechanisms of calcium signals induced by GABAA and GABAB receptor activation in astrocytes. We found that GABA-evoked glial calcium transients are mediated by both GABAA and GABAB receptors. Throughout development, GABA(A)-receptor activation resulted in immediate calcium transients in the vast majority of astrocytes, most likely by influx of calcium through voltage-gated calcium channels. GABAB receptor activation, in contrast, resulted in delayed calcium transients, which were blocked following depletion of intracellular calcium stores and during persistent activation of heterotrimeric G-proteins. GABAB receptor-mediated calcium signals exhibited a clear developmental profile with less than 10% of astrocytes responding at P3 or P32-34, and about 60% of cells between P11 and P15. Our data thus indicate that GABAB receptor-mediated calcium transients are due to calcium release from intracellular stores following Gprotein activation. Moreover, GABAB receptor-mediated calcium signaling in astrocytes preferentially occurs at a period during postnatal development when hippocampal networks are established. (c) 2008 Wiley-Liss, Inc.