Related Experiment Video
Updated: May 16, 2026
Visualizing Shifts on Neuron-Glia Circuit with the Calcium Imaging Technique
Published on: April 8, 2022
Calcium influx through reversed NCX controls migration of microglia
Mami Noda1, Masataka Ifuku, Yuki Mori
1Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. noda@phar.kyushu-u.ac.jp
Abstract:
Microglia, the immune cells of the central nervous system (CNS), are busy and vigilant guards of the adult brain, which scan brain parenchyma for damage and activate in response to lesions. Release of danger signals/chemoattractants at the site of damage initiates microglial activation and stimulates migration. The main candidate for a chemoattractant sensed by microglia is adenosine triphosphate (ATP); however, many other substances can have similar effects. Some neuropeptides such as angiotensin II, bradykinin, endothelin, galanin and neurotensin are also chemoattractants for microglia. Among them, bradykinin increases microglial migration using mechanism distinct from that of ATP. Bradykinin-induced migration is controlled by a G(i/o)-protein-independent pathway, while ATP-induced migration involves G(i/o) proteins as well as mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)-dependent pathway. Galanin was reported to share certain signalling cascades with bradykinin; however, this overlap is only partial. Bradykinin, for example, stimulates Ca(2+) influx through the reversed Na(+)/Ca(2+) exchange (NCX), whereas galanin induces intracellular Ca(2+) mobilization by inositol-3,4,5-trisphosphate (InsP(3))-dependent Ca(2+) release from the intracellular store. These differences in signal cascades indicate that different chemoattractants such as ATP, bradykinin and galanin control distinct microglial functions in pathological conditions such as lesion and inflammation and NCX contributes to a special case of microglial migration.
Insights
Microglia, the brain's immune cells, migrate towards injury sites. Different signals like bradykinin and adenosine triphosphate (ATP) trigger distinct migration pathways, influencing brain repair.
Area of Science:
- Neuroimmunology
- Cellular Neuroscience
Background:
- Microglia are the central nervous system's (CNS) resident immune cells, constantly surveying brain parenchyma.
- Upon detecting damage or lesions, microglia activate and migrate to the affected area, guided by chemoattractants.
Purpose of the Study:
- To investigate the distinct signaling pathways employed by different chemoattractants, such as adenosine triphosphate (ATP) and bradykinin, in mediating microglial migration.
- To elucidate the role of specific ion transport mechanisms, like the Na+/Ca2+ exchanger (NCX), in microglial responses.
Main Methods:
- Comparative analysis of signaling cascades activated by various microglial chemoattractants.
- Investigation of G(i/o)-protein dependency and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways in ATP-induced migration.
- Examination of bradykinin-induced Ca2+ influx via reversed Na+/Ca2+ exchange (NCX) and galanin-induced intracellular Ca2+ release.
Main Results:
- ATP-induced microglial migration involves G(i/o) proteins and the MAPK/ERK pathway.
- Bradykinin triggers microglial migration through a G(i/o)-protein-independent pathway, utilizing Ca2+ influx via reversed Na+/Ca2+ exchange (NCX).
- Galanin signaling partially overlaps with bradykinin but involves distinct intracellular Ca2+ mobilization mechanisms.
Conclusions:
- Different chemoattractants activate distinct intracellular signaling pathways, leading to specialized microglial functions during CNS pathology.
- The Na+/Ca2+ exchanger (NCX) plays a specific role in bradykinin-mediated microglial migration, highlighting pathway divergence.
- Understanding these distinct migratory mechanisms is crucial for developing targeted therapies for CNS lesions and inflammation.
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