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Role of Pericytes in the Initiation and Propagation of Spontaneous Activity in the Microvasculature

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Smooth Muscle Spontaneous Activity

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1124))

Abstract

The microvasculature is composed of arterioles, capillaries and venules. Spontaneous arteriolar constrictions reduce effective vascular resistance to enhance tissue perfusion, while spontaneous venular constrictions facilitate the drainage of tissue metabolites by pumping blood. In the venules of visceral organs, mural cells, i.e. smooth muscle cells (SMCs) or pericytes, periodically generate spontaneous phasic constrictions, Ca2+ transients and transient depolarisations. These events arise from spontaneous Ca2+ release from the sarco-endoplasmic reticulum (SR/ER) and the subsequent opening of Ca2+-activated chloride channels (CaCCs). CaCC-dependent depolarisation further activates L-type voltage-dependent Ca2+ channels (LVDCCs) that play a critical role in maintaining the synchrony amongst mural cells. Mural cells in arterioles or capillaries are also capable of developing spontaneous activity. Non-contractile capillary pericytes generate spontaneous Ca2+ transients primarily relying on SR/ER Ca2+ release. Synchrony amongst capillary pericytes depends on gap junction-mediated spread of depolarisations resulting from the opening of either CaCCs or T-type VDCCs (TVDCCs) in a microvascular bed-dependent manner. The propagation of capillary Ca2+ transients into arterioles requires the opening of either L- or TVDCCs again depending on the microvascular bed. Since the blockade of gap junctions or CaCCs prevents spontaneous Ca2+ transients in arterioles and venules but not capillaries, capillary pericytes appear to play a primary role in generating spontaneous activity of the microvasculature unit. Pericytes in capillaries where the interchange of substances between tissues and the circulation takes place may provide the fundamental drive for upstream arterioles and downstream venules so that the microvasculature network functions as an integrated unit.

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Acknowledgments

The authors are grateful for grant support from the Japan Society for Promotion of the Science (JSPS) (Nos. 21659377, 23659763, 26860521, 16K19361).

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Authors and Affiliations

  1. Department of Cell Physiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan

    Hikaru Hashitani & Retsu Mitsui

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  1. Hikaru Hashitani
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  2. Retsu Mitsui
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Correspondence to Hikaru Hashitani .

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  1. Nagoya City University, Nagoya, Aichi, Japan

    Hikaru Hashitani

  2. Monash University, Melbourne, VIC, Australia

    Richard J. Lang

1 Electronic Supplementary Material

Spontaneous Ca2+ transients and associated constrictions in mural cells. SMCs in a suburothelial venule Venules of the rat bladder develop nearly synchronous spontaneous Ca2+ transients resulting in vasoconstrictions. Note that SMCs in an arteriole run parallel and remain quiescent. Stellate-shaped pericytes in a suburothelial venule of the mouse bladder develop nearly synchronous spontaneous Ca2+ transients and associated vasoconstrictions. Frame rate is 100 ms (AVI 6091 kb)

Spontaneous Ca2+ transients in NG2-DsRed (+) pericytes of PCAs and capillaries. NG2-DsRed (+) pericytes in a PCA Pre-capillary arterioles (PCA) develop synchronous spontaneous Ca2+ transients. NG2-DsRed (+) pericytes in a capillary generate nearly synchronous spontaneous Ca2+ transients. Frame rate is 100 ms (AVI 1166 kb)

Propagation of spontaneous Ca2+ transients in pericytes of capillary/PCA network in the bladder suburothelium. NG2-DsRed (+) pericytes in a capillary network fire spontaneous Ca2+ transients that spread one after another from left to right. Capillary pericytes in a PCA-capillary tree fire spontaneous Ca2+ transients that spread into the PCA to trigger nearly synchronous Ca2+ transients within the PCA-capillary tree. Frame rate is 100 ms (AVI 2730 kb)

Propagation of spontaneous Ca2+ transients in pericytes of myenteric capillary-PCA network in the guinea pig stomach. Pericytes generate nearly synchronous spontaneous Ca2+ transients within a pericyte network in a PCA and branching capillaries. Frame rate is 91 ms. Spontaneous Ca2+ transients generated in pericytes of a PCA Pre-capillary arterioles (PCA) trigger a near-synchronous Ca2+ transient in circumferentially arranged SMCs of an arteriole. Frame rate is 58 ms (AVI 4221 kb)

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Hashitani, H., Mitsui, R. (2019). Role of Pericytes in the Initiation and Propagation of Spontaneous Activity in the Microvasculature. In: Hashitani, H., Lang, R. (eds) Smooth Muscle Spontaneous Activity. Advances in Experimental Medicine and Biology, vol 1124. Springer, Singapore. https://doi.org/10.1007/978-981-13-5895-1_14

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