How Structure, Ca Signals, and Cellular Communications Underlie Function in Precapillary Arterioles

Abstract

Rationale : Precapillary arterioles control blood flow to tissues and their correct function is vital. However, their small size has limited study and little is known concerning the calcium signals in their endothelial and muscle cells and how these relate to function. Objective : We aimed to investigate whether these small vessels are specialized in terms of structure and calcium signaling. Methods and Results : Using in situ confocal imaging we have studied the ultrastructure, Ca signaling and coordination of contraction in precapillary arterioles in ureter and vas deferens. We have compared the data to that from a small mesenteric artery. In the precapillary arteriole, 1 myocyte covers a ≈10-μm length, and contraction of this single cell can decrease the diameter of this segment. In the mesenteric artery, more than 20 myocytes are required for this. In the precapillary arteriole, Ca signals arise solely from Ca release from the sarcoplasmic reticulum through inositol 1,4,5-trisphosphate-induced Ca release and not via ryanodine receptors. Agonist-induced Ca signals do not require Ca entry into the cell, do not spread or synchronize with neighboring cells, and are unaffected by endothelial stimulation, thereby allowing local control. This contrasts with the mesenteric artery, where Ca entry and ryanodine receptors are important and stimulation of the endothelium inhibits myocyte Ca signals and contraction. Conclusions : These data reveal the structural and signaling specializations underlying how blood flow is locally regulated, provide new insight into control of microcirculation, and provide a framework to explain its vulnerability to disease.