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.
Highlights
The entire abluminal surface of the cerebral vasculature is covered by mural cells, namely vascular smooth muscle cells (SMC) and pericytes, which exhibit a continuum of phenotypes
Noteworthy is that in rare cases capillary pericytes (CPs) interconnected vessel segments by extending processes through the parenchyma (Figure 1—figure supplement 1D). These few interconnecting pericytes were excluded from our analysis, since at the time it could not be determined, whether they are remnants of vessel regression or whether they represent a structural feature with importance in neurovascular coupling (Brown, 2010; Alarcon-Martinez et al, 2020; Corliss et al, 2020)
To differentiate between these phenotypically diverse mural cells, we employed a previously coined classification based on microvascular localization: SMC, ensheathing pericytes (EPs), and CP (Grant et al, 2019; Berthiaume et al, 2021)
Summary
The entire abluminal surface of the cerebral vasculature is covered by mural cells, namely vascular smooth muscle cells (SMC) and pericytes, which exhibit a continuum of phenotypes. Pericytes are embedded within the vascular basement membrane and are classically described to have a protruding ‘bump on a log’ cell body with processes that run longitudinally along capillaries (Attwell et al, 2016). Pericytes regulate vascular morphogenesis and maturation as well as maintenance of the blood– brain barrier (Armulik et al, 2011; Armulik et al, 2010; Daneman et al, 2010). In the context of vascular development, several signaling pathways between endothelial cells (EC) and pericytes are important; for instance, in the recruitment of mural cells through platelet-derived growth factor B (PDGFB) and platelet-derived growth factor receptor beta (PDGFRβ) signaling (Gaengel et al, 2009), as well as Angiopoietin/Tie signaling in angiogenesis (Teichert et al, 2017).
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