Extracellular Calcium Depletion in Synaptic Transmission

Regulation of Ca2+ homeostasis in the extracellular space plays an important role in neuronal function. Several modeling studies and recent measurements have demonstrated that modest action potential or synaptic activity can result in a significant reduction in extracellular calcium ([Ca]o(2+)). Changes in [Ca]o(2+) can regulate intracellular signaling enzymes, such as Ca2+/calmodulin-dependent protein kinase II, and influence neuronal function at synaptic and nonsynaptic sites. The change in [Ca]o(2+) can affect several types of ion channels and neurotransmitter receptors and activate a Ca(2+)-sensitive receptor in neuronal membranes. Depletion of [Ca]o(2+) may function as an activity-dependent extracellular messenger that regulates nervous system function during development, learning, and disease.