Synchrony of spontaneous Ca2+ activity in microvascular mural cells

摘要

Spontaneous rhythmic constrictions known as vasomotion are developed in several microvascular beds in vivo . Vasomotion in arterioles is considered to facilitate blood flow, while venular vasomotion would facilitate tissue metabolite drainage. Mechanisms underlying vasomotion periodically generate synchronous Casup2+/sup transients in vascular smooth muscle cells (VSMCs). In visceral organs, mural cells (pericytes and VSMCs) in arterioles, capillaries and venules exhibit synchronous spontaneous Casup2+/sup transients. Since sympathetic regulation is rather limited in the intra-organ microvessels, spontaneous activity of mural cells may play an essential role in maintaining tissue perfusion. Synchronous spontaneous Casup2+/sup transients in precapillary arterioles (PCAs)/capillaries appear to propagate to upstream arterioles to drive their vasomotion, while venules develop their own synchronous Casup2+/sup transients and associated vasomotion. Spontaneous Casup2+/sup transients of mural cells primarily arise from IPsub3/sub and/or ryanodine receptor-mediated Casup2+/sup release from sarcoendoplasmic reticulum (SR/ER) Casup2+/sup stores. The resultant opening of Casup2+/sup-activated Clsup-/sup channels (CaCCs) causes a membrane depolarisation that triggers Casup2+/sup influx via T-type and/or L-type voltage-dependent Casup2+/sup channels (VDCCs). Mural cells are electrically coupled with each other via gap junctions, and thus allow the sequential spread of CaCC or VDCC-dependent depolarisations to develop the synchrony of Casup2+/sup transients within their network. Importantly, the synchrony of spontaneous Casup2+/sup transients also requires a certain range of the resting membrane potential that is maintained by the opening of Ksubv/sub7 voltage-dependent Ksup+/sup (Ksubv/sub7) and inward rectifier Ksup+/sup (Ksubir/sub) channels. Thus, a depolarised membrane would evoke asynchronous, ‘premature’ spontaneous Casup2+/sup transients, while a hyperpolarised membrane prevents any spontaneous activity.