Physiological Reviews, Vol. 81, No. 2, April 2001, pp. 767-806
Copyright ©2001 by the American Physiological Society

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

Institut National de la Santé et de la Recherche Médicale U. 390, Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier, France

Vassort, Guy Adenosine 5'-Triphosphate: a P2-Purinergic Agonist in the Myocardium. Physiol. Rev. 81: 767-806, 2001.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 P2X_1-7 receptors and metabotropic P2Y_1,2,4,6,11 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 G_s protein 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- to produce inositol 1,4,5-trisphosphate and Cl/HCO 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.