Functional role of calcium signals for microglial function.

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• Microglia, the immune cells of the central nervous system, exhibit complex calcium (Ca2+) signaling.
• Current understanding of Ca2+ signaling is primarily derived from cultured microglia, reflecting activated states rather than physiological resting conditions.

Purpose of the Study:

• To review the mechanisms of Ca2+ signaling in microglial cells.
• To elucidate the impact of Ca2+ signaling and intracellular Ca2+ levels on microglial function.

Main Methods:

• Review of existing literature on microglial Ca2+ signaling pathways.
• Focus on ligand-gated channels (purinergic receptors) and intracellular Ca2+ release mechanisms.

Main Results:

• Purinergic receptors are key Ca2+-permeable channels regulating microglial functions like cytokine release.
• Metabotropic receptors trigger Ca2+ release from intracellular stores, followed by capacitative Ca2+ entry.
• Activation, e.g., by endotoxin, leads to chronic intracellular Ca2+ increases, essential for nitric oxide and cytokine release.

Conclusions:

• Ca2+ signaling is fundamental to activated microglial functions, including inflammatory responses.
• Specific signaling pathways, such as purinergic and metabotropic receptor-mediated Ca2+ fluxes, are critical regulators.
• Factors like TNFalpha, IL-1beta, and IFN-gamma modulate basal Ca2+ levels in microglia.