Calcium microdomains in regulated exocytosis

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Calcium ions (Ca2+) are known triggers for exocytosis.
• Theoretical models predicted sub-micrometer Ca2+ domains exceeding 100 microM.
• Early experiments demonstrated Ca2+ microdomains in squid presynaptic terminals.

Purpose of the Study:

• To review the evidence for Ca2+ nano- and microdomains.
• To explore the role of these domains in synaptic vesicle release.
• To discuss the diversity of Ca2+ signaling and release mechanisms across different cell types.

Main Methods:

• Review of experimental findings on Ca2+ signaling.
• Analysis of Ca2+ channel clustering and vesicle arrangements.
• Investigation of Ca2+ sources (influx and intracellular stores).

Main Results:

• Ca2+ microdomains are essential for fast synaptic vesicle release, tightly coupled to action potentials.
• Varied arrangements of vesicles and Ca2+ channels exist in different synapses.
• Ca2+ syntillas (store-operated signals) influence facilitation and spontaneous release.
• Slower Ca2+-evoked exocytosis occurs in peripheral terminals and neuroendocrine cells.
• Non-excitable cells also exhibit localized Ca2+ signaling domains, including Bergmann glia.

Conclusions:

• The geometric arrangement of Ca2+ sources and vesicles dictates the spectrum of Ca2+ signals and release.
• Ca2+ microdomains are fundamental to diverse cellular release processes, from neuronal synapses to glial cells.