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Updated: Jun 16, 2026
Brain Pericyte Calcium and Hemodynamic Imaging in Transgenic Mice In Vivo
Published on: November 20, 2021
Distinct signatures of calcium activity in brain mural cells
Chaim Glück1,2, Kim David Ferrari1,2, Noemi Binini1,2
1Institute of Pharmacology and Toxicology, University of Zurich, Zürich, Switzerland.
Insights
Cortical mural cells, including smooth muscle cells and pericytes, exhibit distinct calcium signaling patterns. Neuronal activation and increased extracellular potassium suppress calcium activity in capillary pericytes.
Area of Science:
- Neuroscience
- Cell Biology
- Vascular Biology
Background:
- Pericytes are crucial for brain health and implicated in neuropathologies.
- Their specific functions and signaling pathways in healthy brains remain largely uncharacterized.
- Cortical mural cells, including smooth muscle cells (SMCs), ensheathing pericytes (EPs), and capillary pericytes (CPs), are key cellular components of the neurovasculature.
Purpose of the Study:
- To characterize the in vivo and in vitro calcium dynamics of cortical mural cells.
- To investigate the differential signaling properties of SMCs, EPs, and CPs.
- To explore the influence of neuronal activity and extracellular potassium on pericyte calcium signaling.
Main Methods:
- Utilized transgenic mice (Pdgfrb-CreERT2;Rosa26LSL-GCaMP6s) for in vivo calcium imaging in anesthetized and awake states.
- Performed calcium imaging in acute brain slices.
- Applied chemogenetic stimulation of neurons and elevated extracellular potassium concentrations.
Main Results:
- SMCs and EPs displayed similar calcium dynamics in vivo, distinct from capillary pericytes (CPs).
- CPs exhibited irregular, high-frequency calcium signals in cellular microdomains, persisting even without vasoconstrictors.
- Neuronal activation and elevated extracellular potassium significantly suppressed CP calcium activity.
Conclusions:
- Cortical mural cells, particularly CPs, possess unique spontaneous calcium signaling properties.
- Neuronal activity and increased extracellular potassium likely suppress CP calcium activity via Kir2.2 and KATP channels.
- These findings shed light on the functional heterogeneity of pericytes and their regulation in the brain.
Abstract:
Pericytes have been implicated in various neuropathologies, yet little is known about their function and signaling pathways in health. Here, we characterized calcium dynamics of cortical mural cells in anesthetized or awake Pdgfrb-CreERT2;Rosa26< LSL-GCaMP6s > mice and in acute brain slices. Smooth muscle cells (SMCs) and ensheathing pericytes (EPs), also named as terminal vascular SMCs, revealed similar calcium dynamics in vivo. In contrast, calcium signals in capillary pericytes (CPs) were irregular, higher in frequency, and occurred in cellular microdomains. In the absence of the vessel constricting agent U46619 in acute slices, SMCs and EPs revealed only sparse calcium signals, whereas CPs retained their spontaneous calcium activity. Interestingly, chemogenetic activation of neurons in vivo and acute elevations of extracellular potassium in brain slices strongly decreased calcium activity in CPs. We propose that neuronal activation and an extracellular increase in potassium suppress calcium activity in CPs, likely mediated by Kir2.2 and KATP channels.
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