Presynaptic roles of intracellular Ca2+ stores in signalling and exocytosis

Author:

Nizami Sohaib1,Lee Vivian W.Y.1,Davies Jennifer1,Long Philip2,Jovanovic Jasmina N.2,Sihra Talvinder S.1

Affiliation:

1. Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, U.K.

2. Department of Pharmacology, School of Pharmacy, University of London, London WC1N 1AX, U.K.

Abstract

The signalling roles of Ca2+ic (intracellular Ca2+) stores are well established in non-neuronal and neuronal cells. In neurons, although Ca2+ic stores have been assigned a pivotal role in postsynaptic responses to Gq-coupled receptors, or secondarily to extracellular Ca2+ influx, the functions of dynamic Ca2+ic stores in presynaptic terminals remain to be fully elucidated. In the present paper, we review some of the recent evidence supporting an involvement of Ca2+ic in presynaptic function, and discuss loci at which this source of Ca2+ may impinge. Nerve terminal preparations provide good models for functionally examining putative Ca2+ic 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 Ca2+ic 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 Ca2+ic store activation may thereby contribute to excitotoxicity and eventual synaptopathy.

Publisher

Portland Press Ltd.

Subject

Biochemistry

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