P2Y2 Receptor-Mediated Ca2+ Signaling and Spontaneous Ca2+ Releases in Human Valvular Myofibroblasts

概要

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Valvular myofibroblasts (VMFs), being the most predominant cells in the cardiac valve, perform a variety of functions to maintain normal valvular physiology. These functions, such as contraction, proliferation, and wound repair, are all directly or indirectly mediated by intracellular Ca2+ concentrations ([Ca 2+]i). Knowing how [Ca2+]i is regulated by vasoactive agents in VMFs enriches the understanding of valvular biology in both health and diseases. In this study we examined the characteristics of purinergic agonist-induced [Ca2+] i responses and observed spontaneous Ca2+ releases in cultured human VMFs. Secondary cultures of human mitral VMFs were incubated with the Ca2+-sensitive fluorescent indicator fura-2 or fluo-4 and visualized with fluorescence microscopy. Both ATP and UTP activated P2Y2 receptors and induced endoplasmic reticulum (ER) Ca2+ release and Ca2+ influx. The lack of [Ca2+]i responses in VMFs challenged with the selective P2Y1 agonists ADPβS and 2-Me-S-ATP further supported that functional P2Y2 receptors are responsible for the Ca2+ signals. Finally, in a small number of VMFs spontaneous Ca2+ releases in localized areas were observed. Blockade of the RyR elongated the latency period between each Ca2+ releasing event, demonstrating the presence of functional RyRs in VMFs.
International Heart Journal刊行会の論文