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

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 P2X1–7 receptors and metabotropic P2Y1,2,4,6,11 receptors 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 3 − exchange to induce a large transient acidosis. No clear correlation is presently possible between an effect and the activation of a given P2-rec...