Presynaptic roles of intracellular Ca2+ stores in signalling and exocytosis

The signalling roles of Ca-IC(2+) (intracellular Ca2+) stores are well established in non-neuronal and neuronal cells. In neurons, although Ca-IC(2+) stores have been assigned a pivotal role in postsynaptic responses to G(q)-coupled receptors, or secondarily to extracellular Ca2+ influx, the functions of dynamic Ca-IC(2+) stores in presynaptic terminals remain to be fully elucidated. In the present paper, we review some of the recent evidence supporting an involvement of Ca-IC(2+) in presynaptic function, and discuss loci at which this source of Ca2+ may impinge. Nerve terminal preparations provide good models for functionally examining putative Ca-IC(2+) stores under physiological and pathophysiological stimulation paradigms, using Ca2+-dependent activation of resident protein kinases as sensors for fine changes in intracellular Ca2+ levels. We conclude that intraterminal Ca-IC(2+) stores may, directly or indirectly, enhance neurotransmitter release following nerve terminal depolarization and/or G-protein-coupled receptor activation. During conditions that prevail following neuronal ischaemia, increased glutamate release instigated by Ca-IC(2+) store activation may thereby contribute to excitotoxicity and eventual synaptopathy.