Homogeneity or heterogeneity, the padadox of neurovascular pericytes in the brain

Pericytes are one of the components of neurovascular unit. They play a critical role in regulating blood flow, blood-brain barrier permeability, neuroinflammation and neuronal activity. In the central nervous system (CNS), pericytes are well classified into three subtypes, i.e. ensheathing, mesh and thin-strand pericytes, in terms of their distinct morphologies and regional-specific distributions. However, whether these three types of pericytes exhibiting heterogeneity or homogeneity regarding of membrane properties has not been well studied to date. Here, we combined bulk RNA sequencing analysis with electrophysiological method to illustrate that three subtypes of pericytes share similar electrical membrane properties in the CNS, suggesting a homogenous perspective of neurovascular pericytes in the brain. In further, we newly identified an inwardly rectifying potassium channel subtype Kir4.1 functionally expressed in pericytes. Electrophysiological patch clamp method identified that Kir4.1 ion channels in pericytes are more sensitive to the elevation of extracellular K+ than that in astrocytes, suggesting that Kir4.1 ion channels in pericytes might play a role of K+ sensor in local neurovascular network in both physiological and pathological conditions.