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

Abstract

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 α7 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.