α7 nicotinic ACh receptors as a ligand-gated source of Ca ²⁺ ions: The search for a Ca ²⁺ optimum

The spatiotemporal distribution of cytosolic Ca ²⁺ ions is a key determinant of neuronal behavior and survival. Distinct sources of Ca ²⁺ ions including ligand- and voltage-gated Ca ²⁺ channels contribute to intracellular Ca ²⁺ homeostasis. Many normal physiological and therapeutic neuronal functions are Ca ²⁺-dependent, however an excess of cytosolic Ca ²⁺ or a lack of the appropriate balance between Ca ²⁺ entry and clearance may destroy cellular integrity and cause cellular death. Therefore, the existence of optimal spatiotemporal patterns of cytosolic Ca ²⁺ elevations and thus, optimal activation of ligand- and voltage-gated Ca ²⁺ ion channels are postulated to benefit neuronal function and survival. Alpha7 nicotinic -acetylcholine receptors (nAChRs) are highly permeable to Ca ²⁺ 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 α7 nAChR-mediated currents and Ca ²⁺ influx and how this source of Ca ²⁺ entry compares to NMDA receptors in supporting cytosolic Ca ²⁺ homeostasis, neuronal function and survival.