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

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.

Keywords: Ca2+-activated chloride channel; Intercellular coupling; Microvasculature; Pericyte; Sarco-endoplasmic reticulum Ca2+ release; Voltage-dependent Ca2+ channel.