α7 Nicotinic ACh Receptors as a Ligand-Gated Source of Ca2+ Ions: The Search for a Ca2+ Optimum

The spatiotemporal distribution of cytosolic Ca2+ ions is a key determinant of neuronal behavior and survival. Distinct sources of Ca2+ ions including ligand-and voltage-gated Ca2+ channels contribute to intracellular Ca2+ homeostasis. Many normal physiological and therapeutic neuronal functions are Ca2+-dependent, however an excess of cytosolic Ca2+ or a lack of the appropriate balance between Ca2+ entry and clearance may destroy cellular integrity and cause cellular death. Therefore, the existence of optimal spatiotemporal patterns of cytosolic Ca2+ elevations and thus, optimal activation of ligand-and voltage-gated Ca2+ ion channels are postulated to benefit neuronal function and survival. Alpha7 nicotinic acetylcholine receptors (nAChRs) are highly permeable to Ca2+ ions and play an important role in modulation of neurotransmitter release, gene expression and neuroprotection in a variety of neuronal and non-neuronal cells. In this review, the focus is placed on a 7 nAChR-mediated currents and Ca2+ influx and how this source of Ca2+ entry compares to NMDA receptors in supporting cytosolic Ca2+ homeostasis, neuronal function and survival.