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P2 Receptors in Cardiac Myocyte Pathophysiology and Mechanotransduction

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出版社

MDPI
DOI: 10.3390/ijms22010251

关键词

cardiac myocyte function; P2X receptors; P2Y receptors; extracellular ATP; mechanical signaling; pathohysiological roles

资金

  1. National Research Foundation of Korea (NRF) - Korean Government (MEST) [2017R1E1A1A01074504]
  2. National Research Foundation of Korea [2017R1E1A1A01074504] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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ATP serves as a major energy source in mammalian cells but also acts as an extracellular chemical messenger through P2 purinergic receptors. Different types of cells release ATP, including neurons, endothelial cells, and muscle cells. Studies have shown the distribution and roles of P2 receptor subtypes in cardiac cells under physiological and pathological conditions, with specific genetic alterations and pharmacological approaches revealing distinct functions of P2 receptors in the heart.
ATP is a major energy source in the mammalian cells, but it is an extracellular chemical messenger acting on P2 purinergic receptors. A line of evidence has shown that ATP is released from many different types of cells including neurons, endothelial cells, and muscle cells. In this review, we described the distribution of P2 receptor subtypes in the cardiac cells and their physiological and pathological roles in the heart. So far, the effects of external application of ATP or its analogues, and those of UTP on cardiac contractility and rhythm have been reported. In addition, specific genetic alterations and pharmacological agonists and antagonists have been adopted to discover specific roles of P2 receptor subtypes including P2X4-, P2X7-, P2Y2- and P2Y6-receptors in cardiac cells under physiological and pathological conditions. Accumulated data suggest that P2X4 receptors may play a beneficial role in cardiac muscle function, and that P2Y2- and P2Y6-receptors can induce cardiac fibrosis. Recent evidence further demonstrates P2Y1 receptor and P2X4 receptor as important mechanical signaling molecules to alter membrane potential and Ca2+ signaling in atrial myocytes and their uneven expression profile between right and left atrium.

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