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The microcirculation is the site of gas and nutrient exchange. Control of central or local signals acting on the myocytes, pericytes and endothelial cells within it, is essential for health. Due to technical problems of accessibility, the mechanisms controlling Ca2+ signalling and contractility of myocytes and pericytes in different sections of microvascular networks in situ have not been investigated. We aimed to investigate Ca2+ signalling and functional responses, in a microcirculatory network in situ. Using live confocal imaging of ureteric microvascular networks, we have studied the architecture, morphology, Ca2+ signalling and contractility of myocytes and pericytes. Ca2+ signals vary between distributing arcade and downstream transverse and precapillary arterioles, are modified by agonists, with sympathetic agonists being ineffective beyond transverse arterioles. In myocytes and pericytes, Ca2+ signals arise from Ca2+ release from the sarcoplasmic reticulum through inositol 1,4,5-trisphosphate-induced Ca2+ release and not via ryanodine receptors or Ca2+ entry into the cell. The responses in pericytes are less oscillatory, slower and longer-lasting than those in myocytes. Myocytes and pericytes are electrically coupled, transmitting Ca2+ signals between arteriolar and venular networks dependent on gap junctions and Ca2+ entry via L-type Ca2+ channels. Endothelial Ca2+ signalling inhibits intracellular Ca2+ oscillations in myocytes and pericytes via L-arginine/nitric oxide pathway and intercellular propagating Ca2+ signals via EDHF. Increases of Ca2+ in pericytes and myocytes constrict all vessels except capillaries. These data reveal the structural and signalling specializations allowing blood flow to be regulated by myocytes and pericytes.

Original publication

DOI

10.1016/j.ceca.2013.06.001

Type

Journal article

Journal

Cell calcium

Publication Date

09/2013

Volume

54

Pages

163 - 174

Keywords

Ca(2+) signalling, Endothelium, Microvascular networks, Myocytes, Pericytes, Animals, Arginine, Arginine Vasopressin, Arterioles, Biological Factors, Calcium, Calcium Signaling, Endothelin-1, Female, In Vitro Techniques, Inositol 1,4,5-Trisphosphate Receptors, Male, Myocytes, Smooth Muscle, Nitric Oxide, Pericytes, Rats, Rats, Wistar, Sarcoplasmic Reticulum, Ureter, Vasomotor System, Venules