Adenosine 5′-Triphosphate: a P2-Purinergic Agonist in the Myocardium

Abstract

ATP, besides an intracellular energy source, is an agonist when applied to a variety of different cells including cardiomyocytes. Sources of ATP in the extracellular milieu are multiple. Extracellular ATP is rapidly degraded by ectonucleotidases. Today ionotropic P2X1–7receptors and metabotropic P2Y1,2,4,6,11receptors have been cloned and their mRNA found in cardiomyocytes. On a single cardiomyocyte, micromolar ATP induces nonspecific cationic and Cl−currents that depolarize the cells. ATP both increases directly via a Gsprotein and decreases Ca2+current. ATP activates the inward-rectifying currents (ACh- and ATP-activated K+currents) and outward K+currents. P2-purinergic stimulation increases cAMP by activating adenylyl cyclase isoform V. It also involves tyrosine kinases to activate phospholipase C-γ to produce inositol 1,4,5-trisphosphate and Cl−/HCO[Formula: see text] exchange to induce a large transient acidosis. No clear correlation is presently possible between an effect and the activation of a given P2-receptor subtype in cardiomyocytes. ATP itself is generally a positive inotropic agent. Upon rapid application to cells, ATP induces various forms of arrhythmia. At the tissue level, arrhythmia could be due to slowing of electrical spread after both Na+current decrease and cell-to-cell uncoupling as well as cell depolarization and Ca2+current increase. In as much as the information is available, this review also reports analog effects of UTP and diadenosine polyphosphates.