Microheterogeneity of calcium signalling in dendrites

Transient changes in the intracellular concentration of free Ca2+ ([Ca2+](i )) originating from voltage- or ligand-gated influx and by ligand- or Ca2+- gated release from intracellular stores, trigger or modulate many fundament al neuronal processes, including neurotransmitter release and synaptic plas ticity. Of the intracellular compartments involved in Ca2+ clearance, the e ndoplasmic reticulum (ER) has received the most attention because it expres ses Ca2+ pumps and Ca2+ channels, thus endowing it with the potential to ac t as both an intracellular calcium sink and store. We review here our ongoi ng work on the role of calcium sequestration into, and release from, En cis terns and the role that this plays in the generation and termination of fre e [Ca2+](i) transients in dendrites of pyramidal neurons in hippocampal sli ces during and after synaptic activity. These studies have been approached by combining parallel microfluorometric measurements of free cytosolic [Ca2 +](i) transients with energy-dispersive X-ray microanalytical measurements of total Ca content within specific dendritic compartments at the electron microscopy level. Our observations support the emerging realization that sp ecific subsets of dendritic ER cisterns provide spatial and temporal microh eterogeneity of Ca2+ signalling, acting not only as a major intracellular C a sink involved in active clearance mechanisms after voltage- and ligand-ga ted Ca2+ influx, but also as an intracellular Ca2+ source that can be mobil ized by a signal cascade originating at activated synapses.