The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes

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Hariharan, AshwiniUniv Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. (author)

The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes

Article/chapterEnglish2020

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2020-12-18
LAUSANNE, SWITZERLAND :Frontiers Media SA,2020
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LIBRIS-ID:oai:DiVA.org:uu-433908
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-433908URI
https://doi.org/10.3389/fncel.2020.601324DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:145569241URI

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Language:English
Summary in:English

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Subject category:for swepub-publicationtype

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Brain pericytes reside on the abluminal surface of capillaries, and their processes cover similar to 90% of the length of the capillary bed. These cells were first described almost 150 years ago (Eberth, 1871; Rouget, 1873) and have been the subject of intense experimental scrutiny in recent years, but their physiological roles remain uncertain and little is known of the complement of signaling elements that they employ to carry out their functions. In this review, we synthesize functional data with single-cell RNAseq screens to explore the ion channel and G protein-coupled receptor (GPCR) toolkit of mesh and thin-strand pericytes of the brain, with the aim of providing a framework for deeper explorations of the molecular mechanisms that govern pericyte physiology. We argue that their complement of channels and receptors ideally positions capillary pericytes to play a central role in adapting blood flow to meet the challenge of satisfying neuronal energy requirements from deep within the capillary bed, by enabling dynamic regulation of their membrane potential to influence the electrical output of the cell. In particular, we outline how genetic and functional evidence suggest an important role for G(s)-coupled GPCRs and ATP-sensitive potassium (K-ATP) channels in this context. We put forth a predictive model for long-range hyperpolarizing electrical signaling from pericytes to upstream arterioles, and detail the TRP and Ca2+ channels and G(q), G(i/o), and G(12/13) signaling processes that counterbalance this. We underscore critical questions that need to be addressed to further advance our understanding of the signaling topology of capillary pericytes, and how this contributes to their physiological roles and their dysfunction in disease.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
pericytes
ion channels
GPCRs (G protein coupled receptors)
neurovascular coupling (NVC)
cerebral blood flow (CBF)
K-ATP channels
brain metabolism

Added entries (persons, corporate bodies, meetings, titles ...)

Weir, NickUniv Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. (author)
Robertson, ColinUniv Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. (author)
He, LiqunUppsala universitet,Vaskulärbiologi,Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, Uppsala, Sweden.(Swepub:uu)liqhe592 (author)
Betsholtz, ChristerUppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Dept Immunol Genet & Pathol, Rudbeck Lab, Uppsala, Sweden.;Karolinska Inst, Dept Med Huddinge MedH, Huddinge, Sweden.;Integrated Cardio Metab Ctr, Huddinge, Sweden.(Swepub:uu)chbet517 (author)
Longden, Thomas A.Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. (author)
Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.Vaskulärbiologi (creator_code:org_t)

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In:Frontiers in Cellular NeuroscienceLAUSANNE, SWITZERLAND : Frontiers Media SA141662-5102

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