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Electrophysiological behavior of microglia
H Kettenmann1, R Banati, W Walz
1Department of Neurobiology, University of Heidelberg, Germany.
Abstract:
The present knowledge of voltage- and ligand-activated ion channels of cultured microglial cells is described and its relevance is discussed. All microglial cells cultured from rat or mouse brain express an inward rectifying K+ channel but no outward currents. This expression is not changed by the length of the cultivation period, nor is it different in freshly isolated cells. It makes the microglial cells distinct from peritoneal macrophages, which possess an outward rectifying K+ channel. In bone marrow, 2 populations of cells could be distinguished electrophysiologically, one with the channel pattern of macrophages and one with that of microglial cells. This finding is interesting in light of the fact that it is presently hypothesized that the differentiation of monocytes into microglia takes place exclusively during embryonic development but not in the adult. The available data thus support the hypothesis that within the bone marrow a population of macrophage precursor cells exists with a possible lineage relationship to brain macrophages. The lack of outward currents in the microglial cells has the functional consequence that even a small inward current leads to a large membrane depolarization, since K+ outward currents are not activated with the depolarization. The microglial cell is thus very sensitive to depolarizing events. We found that ATP induced an inward current and an increase in the conductance, whereas ADP, AMP, and adenosine did not. These relative potencies indicate that microglia possess a P2 purinoceptor linked to an ion channel. The amplitude of the inward current elicited by ATP is about 80 pA and is sufficient to depolarize microglial cells close to 0 mV.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Cultured microglial cells possess unique inward rectifying K+ channels, distinguishing them from macrophages. ATP activates an ion channel via P2 purinoceptors, causing significant microglial cell depolarization.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial cells are key immune cells in the brain.
- Understanding their ion channel properties is crucial for neuroscience and immunology.
- Previous research on microglial ion channels, particularly in culture, is limited.
Purpose of the Study:
- To describe the voltage- and ligand-activated ion channels of cultured microglial cells.
- To discuss the relevance of these ion channel properties.
- To investigate the response of microglial cells to purinergic signaling.
Main Methods:
- Electrophysiological recordings of cultured rat and mouse microglial cells.
- Comparison of ion channel expression with peritoneal macrophages and bone marrow cells.
- Application of ATP, ADP, AMP, and adenosine to assess ligand-activated currents.
Main Results:
- Cultured microglial cells consistently express inward rectifying K+ channels but lack outward currents.
- This ion channel pattern is stable during cultivation and distinct from macrophages.
- ATP, but not other purines, induced an inward current and increased conductance, indicating P2 purinoceptor activation.
- ATP-induced currents were sufficient to depolarize microglial cells significantly.
Conclusions:
- Cultured microglial cells exhibit a unique electrophysiological profile characterized by inward rectifying K+ channels.
- The absence of outward currents renders microglial cells highly sensitive to depolarization.
- Evidence supports the existence of macrophage precursor cells in bone marrow with potential lineage to brain microglia.
- Microglial cells express functional P2 purinoceptors linked to ion channels, activated by ATP.